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Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and the survival outcomes of esophageal cancer patients who underwent esophagectomy, the latest and comprehensive systematic review performed. Methods: Related literature retrieved from PubMed, Web of Science, Embase, and Cochrane before January 2024, according to the inclusion criteria. Outcomes measured were overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and cancer-specific survival (CSS). Results: Eighteen studies with 6,119 esophageal cancer patients were retained for analysis. Meta-analysis demonstrated that OS (HR: 1.47; 95% CI: 1.29, 1.67; P < 0.00001), DFS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001), and CSS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001) were significantly shorter in the high NLR group compared with the low NLR group. In addition, meta-analysis revealed a similar RFS (HR: 1.47; 95% CI: 0.92, 2.35; P = 0.10) among the two groups. Subgroup analysis of OS and DFS based on mean/median age, NLR cutoff, and region found that all subgroups remained significant difference between two groups. Conclusion: Among esophageal cancer patients who underwent esophagectomy, preoperative NLR can be used as prognostic factor independently. High-preoperative NLR is associated with poor prognosis. More large-scale, multicenter prospective clinical studies are needed to further validate the relationship between preoperative NLR and prognosis of esophageal cancer. [ABSTRACT FROM AUTHOR]

Adverse effects and multidrug resistance remain significant obstacles in conventional cancer therapy. Nanomedicines, with their intrinsic properties such as nano-sized dimensions and tunable surface characteristics, have the potential to mitigate the side effects of traditional cancer treatments. While nanomaterials have been widely applied in cancer treatment, challenges such as low targeting efficiency and poor tumor penetration persist. Recent research has shown that anaerobic bacteria exhibit high selectivity for primary tumors and metastatic cancers, offering good safety and superior tumor penetration capabilities. This suggests that combining nanomaterials with bacteria could complement their respective limitations, opening vast potential applications in cancer therapy. The use of bacteria in combination with nanomaterials for anticancer treatments, including chemotherapy, radiotherapy, and photothermal/photodynamic therapy, has contributed to the rapid development of the field of bacterial oncology treatments. This review explores the mechanisms of bacterial tumor targeting and summarizes strategies for synthesizing bacterial-nanomaterial and their application in cancer therapy. The combination of bacterial-nanomaterial hybrids with modern therapeutic approaches represents a promising avenue for future cancer treatment research, with the potential to improve treatment outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs. [ABSTRACT FROM AUTHOR]

Chemotherapy-associated side effects significantly contribute to the challenges of cancer treatment, impacting the well-being of patients and complicating existing conditions. Chemotherapy-induced oedema, characterized by abnormal fluid accumulation and swelling, worsens cancer-related issues, such as impaired wound healing. This oedema may result from drug-induced vascular changes and electrolyte imbalances. Addressing such side effects is crucial for improving prognostic outcomes of cancer patients. The rat paw oedema model is a valuable tool for studying inflammatory oedema, testing novel therapies, and understanding their mechanisms. Conventional treatments for cancer chemotherapy-induced oedema have limitations, highlighting the need for alternative or complementary approaches, such as exploring natural products like Syzygium aromaticum (clove), known for its anti-inflammatory properties and potential to alleviate edema. This study examined the effects of Syzygium aromaticum ethanol extract on inflammatory oedema in rats, identified the responsible active compound (s), and explored the possible mechanism involved through computational modeling. Ethanol extract of Syzygium aromaticum (SAEE) was prepared. In vivo anti-inflammatory activities of the extract were evaluated at a specific controlled timeframe in formalin-induced paw oedema in Wistar rats. The binding affinities and interactions of the initially identified chemical constituents of the extract were modeled, through Glide standard precision and quantum polarized ligand docking, against cyclooxygenase-2 for their potential for their possible inhibitory mechanism. SAEE displayed significant time- and dose-dependent amelioration of inflammatory oedema and dose-dependent inhibition of key proinflammatory cytokines in the rat models. In silico modeling of identified SAEE compounds revealed delphinidin, rhamnetin, and quercetin as responsible for the observed in vivo protective effects of SAEE in rat paw oedema models. This study found that Syzygium aromaticum ethanol extract effectively reduced inflammation-induced paw swelling and modulated key inflammatory markers in the rats, with the inhibitory activities of constituting delphinidin, quercetin, and rhamnetin against cyclooxygenase 2 being possibly responsible for the observed in vivo effects. Further experimental validation and dynamic simulations are needed to confirm their potential potency in more advanced preclinical and clinical models, as well as explore the mechanistic pathways involved. [Display omitted] [ABSTRACT FROM AUTHOR]

• 5-alpha reductase inhibitors may reduce the risk of bladder cancer. • Androgen suppression therapy could improve the prognosis of bladder cancer. • Androgen deprivation therapy did not reduce the incidence of bladder cancer The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the relationship between AST and the incidence or prognosis of BCa. We perform an updated systematic review and meta-analysis utilizing the most recent evidence to investigate the potential influence of AST on the incidence and prognosis of BCa. A comprehensive literature search was performed on the PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases to include potentially eligible studies. Hazard ratios (HR) and odds ratios (OR) were used to calculate the incidence and prognosis of BCa. This meta-analysis included 22 studies with 700,755 participants which investigated the impact of AST on the risk and prognosis of BCa. The pooled results revealed no significant relation between AST and a decreased incidence of BCa (OR: 0.92, 95%CI: 0.77-1.09, P = 0.342). Subgroup analysis reported that patients receiving 5-alpha reductase inhibitors (5-ARIs) exhibited a significantly lower risk of BCa (OR: 0.83, 95%CI: 0.75-0.91, P < 0.001), while androgen deprivation therapy did not show a significant reduction (OR: 1.00, 95%CI: 0.46-2.16, P = 0.995). AST may also significantly improve the recurrence-free survival of patients with BCa (HR: 0.69, 95%CI: 0.50-0.95, P = 0.023). We also detected a significant improvement in OS among BCa patients who received 5-ARIs compared to those without 5-ARIs (HR: 0.82, 95%CI: 0.68-0.99, P = 0.037). No significant correlation was found between AST and a decreased BCa incidence, while 5-ARIs have demonstrated efficacy in reducing BCa occurrence. Moreover, patients who received AST demonstrated improved prognosis. [ABSTRACT FROM AUTHOR]

Nodal status is well known to be the most important prognostic factor for esophageal cancer patients, even if they are treated with neoadjuvant therapy. To establish an optimal postoperative adjuvant strategy for patients, we aimed to more accurately predict the prognosis of patients and systemic recurrence by using clinicopathological factors, including nodal status, in patients with esophageal cancer who received neoadjuvant chemotherapy. The clinicopathological factors associated with survival and systemic recurrence were investigated in 488 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy. Overall survival differed according to tumor depth, nodal status, tumor regression, and lymphovascular (LV) invasion. In the multivariate analysis, nodal status and LV invasion were identified as independent prognostic factors (P  < 0.0001, P  = 0.0008). Nodal status was also identified as an independent factor associated with systemic recurrence, although LV invasion was a borderline factor (P  = 0.066). In each pN stage, patients with LV invasion showed significantly worse overall survival than those without LV invasion (pN0: P  = 0.036, pN1: P  = 0.0044, pN2: P  = 0.0194, pN3: P  = 0.0054). Patients with LV invasion were also more likely to have systemic, and any recurrence than those without LV invasion in each pN stage. Pathological nodal status and LV invasion were the most important predictors of survival and systemic recurrence in patients with esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery. This finding could provide useful information about selecting candidates for adjuvant therapy among these patients. Our analysis showed that LV invasion was an independent prognostic factor in patients with esophageal cancer who underwent neoadjuvant chemotherapy and that combining LV invasion with pathological nodal status makes it possible to stratify the prognosis in those patients. [ABSTRACT FROM AUTHOR]

The number of new cancer cases in Commonwealth countries rose by 35% between 2008 and 2018, but progress in cancer control has been slow in many low-income and lower-middle-income member states. We aimed to examine cancer outcomes and priority areas in the Commonwealth to provide insight and guidance on prioritisation of efforts to improve cancer survival and make the best use of scarce resources. We adapted a previously developed microsimulation model of global cancer survival for 11 cancer sites (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate). All 56 Commonwealth countries were included and classified based on the 2020 World Bank Income groups (low-income, lower-middle-income, upper-middle-income, and high-income countries) and Commonwealth geographical areas. We modelled the number of incident cancer cases in each Commonwealth country in 2020, based on age group-specific estimates of incidence rates from GLOBOCAN 2020. We simulated 5-year net survival for each patient, accounting for the stage at diagnosis (I–IV), availability of specific treatment and imaging modalities, and quality of care (based on residual differences in expected versus observed survival after accounting for the availability and effectiveness of treatment and imaging modalities). We also simulated counterfactual policy scenarios, in which we scaled up various aspects of cancer care to the mean level of high-income countries to estimate the comparative effectiveness of different policies. Incident cancers in the Commonwealth accounted for an estimated 14·3% of global diagnosed cancer cases in 2020 among the 11 cancers modelled (1 610 000 Commonwealth cases [95% UI 1 556 000–1 674 000] of 11 227 000 global cases [11 069 000–11 406 000]) and are estimated to increase to 17·3% in 2050 due to population growth (3 330 000 [3 154 000–3 539 000] of 19 308 000 [18 706 000–19 911 000]). The 5-year net survival across 11 cancers combined in 2020 was 30·7% (95% UI 22·4–38·6) in Commonwealth countries, ranging from 4·1% (0·04–15·2) in low-income countries, 17·8% (3·7–30·9) in lower-middle-income countries, 33·1% (23·7–46·0) in upper-middle-income countries, to 59·0% (57·8–60·2) in high-income countries. Among single treatment policies, scaling up access to radiotherapy had the largest survival impact in low-income countries, surgery had the largest impact in lower-middle-income and upper-middle-income countries, and targeted therapy had the largest impact in high-income countries. By geographical area, improving radiotherapy availability was estimated to have the largest impact in Africa, surgery in Asia, targeted therapy in the Caribbean and the Americas and Europe, and quality of care in the Pacific Commonwealth countries. Comparing packages of scaling up the availability of all treatment modalities versus imaging modalities, expanding availability of imaging yielded the largest benefits in high-income countries, and in the Caribbean and the Americas, Europe, and the Pacific, whereas expanding treatment yielded larger benefits in all other income groups and geographical areas. We found large variation in 5-year net survival, with a nearly 15-times difference in cancer survival by country income group within the Commonwealth. Efforts to improve the availability of treatment and imaging modalities and quality of care will be crucial to reduce these disparities, with specific priorities of scale-up policies varying by setting. The Commonwealth could leverage a broad range of knowledge and resources and have an important role in supporting member countries with setting-specific priorities to improve cancer outcomes. Harvard T H Chan School of Public Health. [ABSTRACT FROM AUTHOR]

Several authors have shown that hematological parameters can be used to detect poor prognosis in patients with cancer. Thus, such features could be used in artificial intelligence (AI-based) models to predict mortality among these patients. This work aimed to develop and compare several AI-based models to predict the prognosis (death vs. survival) of cancer in patients using blood tests and patient data as inputs. At total, 908 cancer patients were assisted in a prospective study. Four artificial intelligence models were compared: artificial neural networks (ANN), supporting vector machines (SVM), decision trees and neuro-fuzzy networks. Also, four different input strategies were tested, considering the use of 49, 45, 22 and 14 inputs. The results of this study showed that the ANN and the SVM presented the best results, using 45 inputs. The ANN was the best model since it presented better statistical values for the positive (death) and negative (survival) classes. The use of blood parameters as inputs for AI-based models could be used to predict death in patients with cancer, and this methodology can be expanded to other diseases. [ABSTRACT FROM AUTHOR]

Gender-specific differences in the diagnostics and treatment must be considered for various lung diseases. In the case of pneumothorax, in addition to differences in etiology there are also relevant differences in treatment and recurrence rates between men and women. For example, to achieve low recurrence rates catamenial pneumothorax requires interdisciplinary collaboration with gynecology. The incidence of lung cancer has equalized in recent years and in addition, various gender-specific prognostic factors have become relevant. Several meta-analyses have identified female gender as a positive prognostic factor for lung cancer, in addition to the higher prevalence of various driver mutations in women. In current trials of multimodal treatment for lung cancer, gender differences in tolerability and patient outcome are already apparent. In subgroup analyses better event-free survival was observed in women, although immune-mediated adverse events were more common in women. [ABSTRACT FROM AUTHOR]

• We conducted this meta -analysis based on relevant protocols, showed a complete overview of the available data in terms of prognostic value of HPV cell-free DNA in cervical cancer. • This study demonstrated that cervical cancer patients with positive HPV cell-free DNA detection at end of treatment had significantly worse oncological outcomes compared with that of negative patients. • Personalized monitoring of HPV cell-free DNA is expected to be a promising prognostic biomarker for cervical cancer patients. This meta -analysis aimed to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients. Searches were performed in MEDLINE, Embase, and CENTRAL from their inception until 26 November 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients according to the levels of HPV cell-free DNA. Data extraction and study quality assessment were performed independently by two authors. Pooled hazard ratios and 95% confidence intervals were calculated using the inverse-variance method for survival outcomes. Five studies were finally included in this meta -analysis. Blood samples were collected from 167 patients before treatment, with 150 individuals available for analysis at the end of treatment. Furthermore, 82 patients with available samples at 3 months post-treatment were included in the analysis. The pooled results indicated a significant association between positive HPV cell-free DNA at end of treatment and worse progression-free survival in patients with cervical cancer (pooled hazard ratio: 5.49; 95 % confidence interval: 2.85–10.58; I2: 0 %). Similar findings were observed in patients with detectable HPV cell-free DNA at 3 months post-treatment (pooled hazard ratio: 7.86; 95 % confidence interval: 3.32–18.60; I2: 0 %). However, the detection of HPV cell-free DNA before treatment was not significantly associated with progression-free survival (pooled hazard ratio: 0.97; 95 % confidence interval: 0.55–1.71; I2: 0 %). Cervical cancer patients testing positive for HPV cell-free DNA at the end of treatment or 3 months post-treatment displayed significantly poorer oncological outcomes compared to those testing negative. Thus, personalized monitoring of HPV cell-free DNA holds promise as a prognostic biomarker for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Gallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes. Patients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41–60 years), group 3(>60 years) and their outcomes were compared. Total of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS. Gallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). Methods: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)‐adjusted Kaplan–Meier curves for non‐urinary tract recurrence‐free survival (NUTRFS), cancer‐specific survival (CSS), and overall survival (OS). Interaction terms within IPTW‐adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien‐Dindo grade 3 or higher) was analyzed. Results: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107‐month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: −6.8 to 7.3]; CSS, 1.2 [−4.9 to 7.3]; OS, 0 [−6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). Conclusions: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR‐associated factors, and (2) PU was associated with unfavorable perioperative outcomes. [ABSTRACT FROM AUTHOR]

Aims: The prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short‐ and long‐term outcomes in patients with CRC. Methods: This was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease‐free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection. Results: Increased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease‐free and overall survival. Similar outcomes were observed in a subanalysis focused on high‐risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score‐matching analysis validated the impact of IBI on the prognosis in CRC patients. Conclusion: We established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow‐up. [ABSTRACT FROM AUTHOR]

Background: The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been associated with prognosis in patients with hepatocellular carcinoma (HCC). We hypothesized that dynamic changes in CXI might be associated with long‐term outcomes in HCC. Methods: This study comprised 131 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Preoperative CXI (pre‐CXI) and postoperative CXI (post‐CXI) were calculated by the following formula: skeletal muscle index x serum albumin level / neutrophil‐to‐lymphocyte ratio. Pre‐ and post‐CXI were classified into two groups (high vs. low). We retrospectively investigated the association of perioperative dynamic changes in CXI with disease‐free and overall survival. Results: In multivariate analyses, negative HBs‐antigen (p = 0.02), high serum PIVKA‐II level (p < 0.01), poor tumor differentiation (p = 0.02), multiple tumors (p < 0.01), microvascular invasion (p < 0.01), partial resection (p < 0.01), postoperative complications (p < 0.01), and low‐pre‐CXI (p < 0.01) were significant predictors of disease‐free survival, while high ICGR15 (p = 0.01), poor tumor differentiation (p < 0.01), multiple tumors (p = 0.01), postoperative complications (p < 0.01), low‐pre‐CXI (p < 0.01), and low‐post‐CXI (p < 0.01) were significant predictors of overall survival. Low‐post‐CXI was associated with older age (p = 0.045), larger tumor (p < 0.01), longer operation time (p = 0.047), greater intraoperative bleeding (p < 0.01), and intraoperative blood transfusion (p < 0.01). Moreover, dynamic changes in CXI were associated with overall survival in each subgroup of patients with low‐pre‐CXI (p = 0.02) or high‐pre‐CXI (p = 0.03). Conclusions: Not only post‐CXI but also dynamic changes in CXI from pre‐ to post‐hepatectomy can be a prognostic indicator of HCC, providing a compelling rationale for aggressive perioperative nutritional and physical interventions to improve long‐term outcomes. [ABSTRACT FROM AUTHOR]

Background: The European Society for Medical Oncology (ESMO) guidelines are among the most comprehensive and widely used clinical practice guidelines (CPGs) globally. However, the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated. This study assessed ESMO CPG levels of evidence (LOE) and grades of recommendations (GOR), as well as their trends over time across various cancer settings. Methods: We manually extracted every recommendation with the Infectious Diseases Society of America (IDSA) classification from each CPG. We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types. Results: Among the 1,823 recommendations in the current CPG, 30% were classified as LOE I, and 43% were classified as GOR A. Overall, there was a slight decrease in LOE I (-2%) and an increase in the proportion of GOR A (+1%) in the current CPG compared to previous versions. The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials (LOE I-II) shows a decrease (71% vs. 63%, p = 0.009) while recommendations based on lower levels of evidence (LOE III-V) show an increase (29% vs. 37%, p = 0.01) between previous and current version. In the current versions, the highest proportion of LOE I (42%) was found in recommendations related to pharmacotherapy, while the highest proportion of GOR A recommendations was found in the areas of pathology (50%) and diagnostic (50%) recommendations. Significant variability in LOE I and GOR A recommendations and their changes over time was observed across different cancer types. Conclusion: One-third of the current ESMO CPG recommendations are supported by the highest level of evidence. More well-designed randomized clinical trials are needed to increase the proportion of LOE I and GOR A recommendations, ultimately leading to improved outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Osteosarcoma (OS) is a primary bone tumor with high malignancy and poor prognosis. Ferroptosis plays a crucial role in OS. This study aimed to evaluate the effects of Ankyrin 1 (ANK1) on OS and to investigate its specific mechanisms. Methods: Microarray datasets related to "osteosarcoma" were selected for this study. Relevant hub genes in OS were identified through bioinformatics analysis. Transfected U-2OS and MG-63 cells were used for in vitro experiments. The effects of ANK1 overexpression on cell viability, migration, and invasion were determined through CCK-8, wound healing, and transwell assays. An OS mouse model was established for the in vivo experiments. Hematoxylin-eosin staining and immunohistochemistry were conducted to observe the histological effects of ANK1 overexpression on mouse tumors. TUNEL staining was performed to evaluate apoptosis in mouse. Results: There were 159 common differentially expressed genes in the GSE16088 and GSE19276 datasets. The hub genes ANK1, AHSP, GYPB, GYPA, KEL, and ALAS2 were identified. Pan-cancer analysis verified that ANK1 was closely associated with cancer prognosis and immune infiltration. Furthermore, ANK1 overexpression inhibited the proliferation, migration, and invasion of OS cells and promoted ferroptosis, while ferroptosis inhibitor (fer-1) weakened these effects. Moreover, ANK1 overexpression suppressed tumor growth, promoted apoptosis, reduced the number of Ki67 positive cells, and elevated the number of caspase-3 positive cells in vivo. Conclusions: ANK1 is a prognosis biomarker of OS that can alleviate the progression of OS by promoting ferroptosis. [ABSTRACT FROM AUTHOR]

HERC5, a vital protein in the HERC family, plays crucial roles in immune response, cancer progression, and antiviral defense. This bioinformatic study comprehensively assessed HERC5's significance across various malignancies by analyzing its gene expression, immune and molecular subtype expressions, target proteins, biological functions, and prognostic and diagnostic values in pan‐cancer. We further examined its correlation with clinical features, co‐expressed and differentially expressed genes, and prognosis in clinical subgroups, focusing on endometrial cancer (UCEC). Our findings showed that HERC5 RNA is expressed at low levels in most cancers and significantly differs across immune and molecular subtypes. HERC5 accurately predicts cancer and correlates with most cancer prognoses. In UCEC, HERC5 was significantly associated with age, hormonal status, clinical stage, treatment status, and metastasis. Elevated HERC5 expression was linked to worse progression‐free interval, disease‐specific survival, and overall survival in UCEC, particularly in diverse clinical subgroups. Significant differences in HERC5 expression were also observed in various human cancer cell line validations. In summary, HERC5 may be a critical biomarker for pan‐cancer prognosis, progression, and diagnosis, as well as a promising new target for cancer therapy. [ABSTRACT FROM AUTHOR]

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan–Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial–mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions The role of the zinc fingers and homeoboxes family (ZHX1–3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues.Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (n = 33), hepatitis C (n = 16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (n = 5). Next‐generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan–Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors.High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus‐associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation‐negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation‐positive HCC and HCC patients over 70 years old.These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC. [ABSTRACT FROM AUTHOR]

Coping with cancer presents a multitude of challenges that encompass every aspect of a patient's life. These challenges not only strain the body but also weigh heavily on the mind, often culminating in profound psychological distress for cancer patients. The cumulative burden of these experiences can heighten the risk of developing psychiatric disorders, exacerbating the already daunting landscape of cancer care. Therefore, this study reviewed the available research with the aim of investigating the effects of traditional Chinese medicine on psychological conditions in elderly cancer patients. In this scoping review, we applied specific criteria to select studies that focused on elderly patients with cancer. We performed an extensive search across electronic databases, including Embase, Science Direct, PubMed, Google Scholar, Scopus, Cochrane Library and Web of Science. In our investigation, we identified a total of 3870 articles related to the topic under review. Following a meticulous screening process that involved evaluating titles, abstracts, and full texts, we ultimately selected five articles deemed relevant for inclusion in this review. Among these articles, three were randomised studies, while the remaining two were review articles. The outcomes of our analysis revealed that herbal decoctions, nutritional counselling, Tai Chi and acupressure, can effectively improve various psychological outcomes in elderly cancer patients. These interventions reduce fatigue, depression, anxiety, and stress, while also enhancing sleep quality and overall mental health. The present study highlights the importance of traditional Chinese medicine in addressing the needs of elderly patients with cancer. As a result, it is recommended that further extensive research be conducted to comprehensively assess the efficacy and safety of traditional Chinese medicine in managing cancer in the elderly. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50–80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common gynecological malignancy; however, there is no useful blood diagnostic biomarker. This study aimed to determine the utility of tissue factor pathway inhibitor 2 (TFPI2), a biomarker of ovarian cancer, as a diagnostic marker for endometrial cancer. Methods: We examined serum TFPI2 levels in patients with endometrial cancer (n = 328) compared to those in healthy controls (n = 65) and evaluated the performance of serum TFPI2 levels as a diagnostic marker. We investigated the clinicopathological characteristics of patients with TFPI2-negative and TFPI2-positive endometrial cancer. Using immunohistochemistry (IHC), we examined TFPI2 expression in tumor tissues of 105 patients with type II endometrial carcinoma and evaluated the correlation between serum and tissue TFPI2 positivity. Results: Patients with endometrial cancer had significantly higher serum TFPI2 levels than controls (196.7 pg/mL vs. 83.3 pg/mL; p < 0.001). The sensitivity and specificity were 54.3% and 95.4%, respectively (cutoff value, 191 pg/mL). Serum TFPI2 levels were significantly elevated along with the stage progression (stage I, 189.6 pg/mL; stage III, 230.9 pg/mL; stage IV, 312.5 pg/mL; p < 0.001). Patients with high-risk histology showed significantly elevated serum TFPI2 levels than those with low-risk histology (220.8 pg/mL vs. 187.7 pg/mL; p < 0.001). The positivity rate for TFPI2 was the highest among tumor markers, including CA125, CA19-9, and CEA. Serum TFPI2 and CA125 levels were almost independent (r = 0.203, p < 0.001), and the combined sensitivity increased to 58.8%. The 5-year survival rate was significantly worse in TFPI2-positive patients (≥ 191 pg/mL, n = 178) than in TFPI2-negative patients (< 191 pg/mL, n = 150) (hazard ratio, 8.22; 95% confidence interval, 2.49–27.1; p < 0.001). TFPI2 immunostaining revealed that 37.1% (39/105) of the samples were positive for TFPI2, with an IHC score of > 0. There was no significant difference in the immunostaining score according to histological type. Serum TFPI2 levels and immunostaining score showed poor agreement (kappa coefficient, -0.039). Conclusions: The serum TFPI2 level is a promising marker for diagnosing and predicting the prognosis of endometrial cancer. No correlation exists between serum and tissue TFPI2 levels. Further multicenter clinical trials are needed to test the utility of TFPI2 as a diagnostic marker. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphisms (SNPs) in DNA repair genes can impair protein function and hinder DNA repair, leading to genetic instability and increased cancer risk. The Excision Repair Cross-Complementation (ERCC) family plays a crucial role in nucleotide excision repair, yet their comprehensive multi-omics characterization and roles in tumor prognosis and immune microenvironment remain unexplored. Methods and materials: We performed bioinformatics analysis using publicly available data from 33 cancer types to investigate associations between ERCC gene expression, patient prognosis, and clinical features. We also validated the role of ERCC2 in bladder cancer through in vitro assays, including CCK-8, colony formation, wound healing, and Transwell assays. Results: By utilizing the most recent database, we have conducted an analysis that reveals associations between variations in ERCC expression across multiple cancer types and both patient prognosis and the tumor microenvironment. To ensure the reliability of our findings, we applied the Benjamini-Hochberg procedure to adjust for multiple testing. After correction, we identified that ERCC expression levels remained significantly correlated with patient prognosis in various cancer types (p < 0.05). In addition, according to the results of drug sensitivity studies of anticancer drugs, there is a large correlation between ERCC expression and the sensitivity of different anticancer drugs. Finally, in vitro cell behavioral assays determined that knockdown of ERCC2 gene expression significantly inhibited the proliferation, migration and invasion of bladder cancer cells. Conclusion: Through in-depth exploration of ERCC differential expression and its correlation with immune-related indicators, the unique microenvironment of tumors, and patient prognosis, we verified the potential role of ERCC2 in the process of bladder cancer genesis and progression. Therefore, we believe that the ERCC family of genes is expected to be a new option for cancer treatment and deserves to be further explored in the future. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) are mediators between cancer cells and other types of cells, such as tumor-associated macrophages (TAMs), in the tumor microenvironment. EVs can remodel the tumor microenvironment and regulate tumor progression. However, the underlying molecular mechanism of these interactions remains unclear. Methods: First, we explored the effect of TAMs on the survival prognosis of patients with ovarian cancer. Next, we isolated EVs derived from ovarian cancer cells (OV-EVs) through ultracentrifugation and analyzed the capacity of OV-EVs to regulate macrophage polarization in ovarian tumors and in whole peripheral blood. Moreover, we explored the roles of OV-EVs-induced macrophages in tumor progression through in vitro and in vivo assays. Results: OV-EVs were encapsulated by macrophages and induced the polarization of macrophages toward the M2 phenotype. Moreover, OV-EVs-induced M2 macrophages promoted angiogenesis and cancer progression both in vitro and in vivo. In addition, OV-EVs-induced macrophages increased the expression level of VEGF and increased the expression level of VEGFR in tumors, which resulted in angiogenesis in ovarian cancer. Conclusions: The present study demonstrated that OV-EVs induce M2 polarization in macrophages and promote the progression of ovarian cancer. This study provides novel insight into the mechanism of ovarian cancer progression. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion We retrospectively studied young patients with head and neck squamous cell carcinoma (HNSCC) to identify factors associated with disease‐specific survival (DSS).Patient and tumor characteristics of patients aged ≤45 who received treatments for non‐metastatic HNSCC were collected to identify factors associated with DSS. Proportional hazards regression was applied separately for surgical and non‐surgical patients.230 patients were included. Surgical and non‐surgical patients had similar DSS. Higher pathologic stages, positive margins, perineural invasion (PNI), extranodal extension and negative HPV status were associated with worse DSS for surgical patients and negative HPV status for non‐surgical patients. In the multivariate analysis, pathologic stages, positive margins, and PNI were associated with worse DSS in surgical patients.Pathologic stages, positive margins, and PNI are independently associated with worse DSS in young surgical HNSCC patients. PNI is a uniquely strong prognostic factor for young patients. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSThe role of tweety homolog 3 (TTYH3) has been studied in several cancers, including hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. The results showed that TTYH3 is highly expression in cervical cancer tissues and cells and high TTYH3 expression correlates with poor prognosis in patients with cervical cancer. TTYH3 markedly reduced the apoptosis rate and promoted proliferation, migration, and invasion. Silencing of TTYH3 has been shown to have an inhibitory effect on cervical cancer progression. Moreover, TTYH3 enhanced EMT and activated Wnt/β-catenin signaling. Furthermore, TTYH3 knockdown inhibited the tumor growth in vivo. In conclusion, TTYH3 promoted cervical cancer progression by activating the Wnt/β-catenin signaling.TTYH3 is upregulated in cervical cancer tissue and cells.TTYH3 promotes cervical cancer cell proliferation.TTYH3 inhibits cervical cancer cell apoptosis.TTYH3 induces cervical cancer cell migration and invasion.TTYH3 activates the Wnt signaling in cervical cancer cell. [ABSTRACT FROM AUTHOR]

AbstractCancer cachexia, characterized by the progressive loss of skeletal muscle mass, leads to functional impairment and poor prognosis. Anamorelin is approved for treating cancer cachexia in Japan; however, the factors influencing its discontinuation and the impact of combining anamorelin with rehabilitation remain unclear. Therefore, we retrospectively analyzed 82 patients with cancer cachexia to identify factors associated with anamorelin discontinuation and assess changes in nutritional status and motor function using non-dominant handgrip strength after 12 wk. Patients received outpatient rehabilitation, combining resistance and aerobic training every two weeks, alongside anamorelin therapy. Our findings indicate that patients with an ECOG performance status of 1 or 2 were less likely to continue anamorelin therapy for 12 wk compared to those with a performance status of 0 (odds ratio 2.71; 95% CI 1.05 − 7.00; p = 0.040). Significant improvements were observed in body weight (48.8 to 53.7 kg, p < 0.001), skeletal muscle mass (6.4 to 6.9 kg/m2, p < 0.001), FAACT score (11.5 to 18.0, p < 0.001), and non-dominant handgrip strength (20.5 to 21.7 kg, p = 0.018) after 12 wk. Early initiation of anamorelin with regular rehabilitation is recommended to enhance nutritional status and motor function in patients with cancer cachexia. [ABSTRACT FROM AUTHOR]

Background: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). Methods: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). Conclusions: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells.Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies.Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53.This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients. [ABSTRACT FROM AUTHOR]

Background: Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of TOX with The Cancer Genome Atlas (TCGA) Pancancer Data. Methods: TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the “CIBERSORT” method. The correlation between TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay. Results: In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore, TOX clearly impacted the viability of cancer cells. Conclusions: TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs. [ABSTRACT FROM AUTHOR]

Background/Objectives: The textbook outcome (TO) is a composite tool introduced to uniform surgical units and regulate surgical quality and outcomes. A patient is considered TO only if all predetermined items are met. In colorectal surgery, TO represents a new tool that can achieve important results given the prevalence of colorectal cancers. However, at present, there is a lack of uniformity in the TO's definition. This study utilized the Delphi process to define an Italian version of the TO in colorectal cancer. Methods: The survey consisted of two rounds of online questionnaires submitted to an expert panel in colorectal oncological surgery, renowned academic surgeons, who had attended multiple scientific conferences and who were authors of papers on this specific topic. Five main topics with 26 questions were investigated through an online modified Delphi method. Items with almost 75% agreement achieved consensus. Results: Twenty-eight Italian experts were selected and participated in the two rounds. The Italian version of the textbook outcome in colorectal surgery was defined as the presence of 90-day postoperative survival, negative margins and at least 12 lymph nodes, a minimally invasive approach, ostomy fashioning if preoperatively planned, postoperative complication < Clavien–Dindo 3b, at least 10 ERAS items, no readmission, proper CHT and RT regimens, complete colonoscopy after or before surgery and Tumor Board Evaluation. Conclusions: The textbook outcome in colorectal cancer patients is a quality instrument providing a complete overview of the care of such patients, from diagnosis to treatment. We hereby propose an Italian version of the TO with outcomes chosen by an expert panel. [ABSTRACT FROM AUTHOR]

Background: Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. Methods: Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. Results: CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. Conclusion: Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Intramedullary nailing spanning from the proximal to distal femur is a well-accepted orthopedic surgical technique for patients with metastatic cancer in the diaphysis of the femur. However, in the new era of precision cancer care and improved survival, there is a critical need to address cancer progression after reaming and insertion of a nail through the cancer-laden bone. We aim to characterize rates of cancer progression following long nailing and subsequent salvage techniques for patients with progression. We also present a novel rod-retaining percutaneous salvage using radiofrequency ablation and cementoplasty to delay or prevent open surgery which may not be favorable for advanced-stage cancer patients. We find that 14% of nailing patients experience progression. Percutaneous salvage showed promising improvements in pain and ambulatory scores and avoided the need for open surgery in most patients. Overall, cancer progression does occur following nailing and continued monitoring, and timely intervention is required to prevent nail or bone breakage. Intramedullary nailing insertion from the proximal-to-distal femur is frequently performed for impending and complete pathological femur fractures due to osteolytic metastases. After nailing through cancer-laden bone, residual chemotherapy- and/or radiation-resistant tumor may progress. Progression of osteolysis risks future nail failure or pathological fractures. This study assesses the incidence of cancer progression following intramedullary nailing in a femur-only cohort and describes a percutaneous rod-retaining salvage technique. A single-institution, retrospective study was conducted to identify adult patients who underwent intramedullary nailing for femoral osteolytic lesions for complete or impending nail failure from 2016 to 2023. Progression was defined as enlargement of the pre-existing lesion and/or appearance of new lesions on radiographs. Surgical outcomes were assessed with a combined pain and functional score. A total of 113 patients (median age 66.8 years (IQR = 16.4); median follow-up 6.0 months (IQR = 14.5)) underwent intramedullary nailing. Sixteen patients (14.2%) exhibited post-nailing cancer progression. Pre- and postoperative radiation and chemotherapy did not decrease the odds of cancer progression. Three patients underwent initial open surgical salvage consisting of proximal femur replacement arthroplasty, and six patients did not receive salvage due to poor surgical candidacy or patient choice. Seven patients (median follow-up 10.7 months (IQR = 12.9)) received percutaneous salvage. In this group, pain and functional scores improved by 4.0 points (p = 0.0078) at two-week postoperative follow-up and 2.0 points (p = 0.0312) at the most recent follow-up (mean follow-up 13.0 ± 9.4 months). All three nonambulatory patients became ambulatory, and six patients were able to ambulate independently without walking aids. No major complications were reported 30 days postoperatively. Progression of femoral osteolytic metastases may occur following intramedullary nailing. Continued monitoring of the entire femur is needed to maintain improved functional status and to prevent catastrophic progression of pre-existing lesions or appearance of new lesions. In patients with more proximal metastases only, the customary practice of bringing a long nail from the proximal femur to distal metaphysis should be reconsidered. Furthermore, there is concern of mechanical transport of cancer cells during guide wire insertion, reaming, and rod insertion through cancer laden bone to cancer free distal bone. [ABSTRACT FROM AUTHOR]

Background: Disulfidptosis is a newly identified mechanism of cell death triggered by disulfide stress. Thus, gaining a comprehensive understanding of the disulfidptosis signature present in gastric cancer (GC) could greatly enhance the development of personalized treatment strategies for this disease. Methods: We employed consensus clustering to identify various subtypes of disulfidptosis and examined the distinct tumor microenvironment (TME) associated with each subtype. The Disulfidptosis (Dis) score was used to quantify the subtype of disulfidptosis in each patient. Subsequently, we assessed the predictive value of Dis score in terms of GC prognosis and immune efficacy. Finally, we conducted in vitro experiments to explore the impact of Collagen X (COL10A1) on the progression of GC. Results: Two disulfidptosis-associated molecular subtypes (Discluster A and B) were identified, each with distinct prognosis, tumor microenvironment (TME), immune cell infiltration, and biological pathways. Discluster A, characterized by high expression of disulfidptosis genes, exhibited a high immune score but poor prognosis. Furthermore, the Dis score proved useful in predicting the prognosis and immune response in GC patients. Those in the low Dis score group showed better prognosis and increased sensitivity to immunotherapy. Finally, our experimental findings validated that downregulation of COL10A1 expression attenuates the proliferation and migration capabilities of GC cells while promoting apoptosis. Conclusions: This study demonstrates that the disulfidptosis signature can assist in risk stratification and personalized treatment for patients with GC. The results offer valuable theoretical support for anti-tumor strategies. [ABSTRACT FROM AUTHOR]

ERβ has been assigned a tumor suppressor role in many cancer types. However, as conflicting findings emerge, ERβ's tissue-specific expression and functional role have remained elusive. There remains a notable gap in compact and comprehensive analyses of ESR2 mRNA expression levels across diverse tumor types coupled with an exploration of its potential gene network. In this study, we aim to address these gaps by presenting a comprehensive analysis of ESR2 transcriptomic data. We distinguished cancer types with significant changes in ESR2 expression levels compared to corresponding healthy tissue and concluded that ESR2 influences patient survival. Gene Set Enrichment Analysis (GSEA) distinguished molecular pathways affected by ESR2, including oxidative phosphorylation and epithelial–mesenchymal transition. Finally, we investigated genes displaying similar expression patterns as ESR2 in tumor tissues, identifying potential co-expressed genes that may exert a synergistic effect on clinical outcomes, with significant results, including the expression of ACIN1, SYNE2, TNFRSF13C, and MDM4. Collectively, our results highlight the significant influence of ESR2 mRNA expression on the transcriptomic landscape and the overall metabolism of cancerous cells across various tumor types. [ABSTRACT FROM AUTHOR]

Background: Hypoxia-regulated proteins (HIF-1α and GLUT-1) have been identified as prognostic markers in various cancers; however, their role in endometrial cancer remains unclear. This study aimed to evaluate HIF-1α and GLUT-1 expression in endometrial cancer and correlate their expression with clinicopathological features. Materials and Methods: A tissue microarray (TMA) was constructed using specimens from a retrospective cohort of 51 endometrial cancer patients who underwent hysterectomy at the Gyeongsang National University Hospital between 2002 and 2009. Clinicopathologic data were collected from electronic medical records, and HIF-1α and GLUT-1 expressions were assessed in the tumor tissue. Results: GLUT-1 expression in endometrial cancer was categorized as mosaic, central, or diffuse. Most patients (56.0%) exhibited a central pattern, followed by diffuse (32.0%) and mosaic (12.0%) patterns. GLUT-1 expression was not significantly associated with histologic grade (p = 0.365). HIF-1α expression in immune cells, but not tumor cells, was significantly associated with a higher histologic grade. A higher proportion of HIF-1α-positive immune cells, using both thresholds (≤1% vs. >1% and ≤5% vs. >5%), was significantly associated with higher histologic grade (p = 0.032 and p = 0.048, respectively). In addition, a higher proportion of HIF-1α-positive immune cells was significantly associated with a diffuse GLUT-1 expression pattern using >5% as a threshold. There were no significant differences in the proportion of HIF-1α-positive immune cells between groups stratified by age, tumor size, or invasion depth, regardless of whether the 1% or 5% threshold for HIF-1α positivity was used. Conclusions: A higher proportion of HIF-1α-positive immune cells is associated with endometrial cancers with higher histologic grade and diffuse GLUT1 expression patterns. These findings suggest a potential role for HIF-1α as a prognostic marker and highlight the need for further studies into the role of HIF-1α in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a deadly disease worldwide. The relationship between HF and cancer remains poorly understood. The Gene Expression Omnibus database was used to download the RNA sequencing data of 356 patients with hypertrophic cardiomyopathy-induced HF and non-HF. A co-expression network was established through the weighted correlation network analysis (WGCNA) to identify hub genes of HF and cancer. Cox risk analysis was performed to predict the prognostic risks of HF hub genes in pan-cancer. HF was linked to immune response pathway by the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A positive correlation was observed between the expression levels of 4 hub genes and the infiltration of CD8+T-cells in pan-cancer. 4 hub genes were identified as beneficial prognostic factors in several cancers. Western blotting and real-time polymerase chain reaction validated the high expression of GZMM, NKG7, and ZAP70 in both mice and patients with HF compared to control groups. Our study highlights the shared immune pathogenesis of HF and cancer and provides valuable insights for developing novel therapeutic strategies, offering new opportunities for improving the management and treatment outcomes of both HF and cancer. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies. [ABSTRACT FROM AUTHOR]

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Background: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients. Methods: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0. Results: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45–2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42–2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup. Conclusions: TBS may be an efficient prognostic index in HCC patients. [ABSTRACT FROM AUTHOR]

The Gasdermin E gene (GSDME) plays roles in deafness and cancers. However, the roles and mechanisms in cancers are complex, and the same gene exhibits different mechanisms and actions in different types of cancers. Online databases, such as GEPIA2, cBioPortal, and DNMIVD, were used to comprehensively analyze GSDME profiles, DNA methylations, mutations, diagnosis, and prognosis in patients with tumor tissues and matched healthy tissues. Western blotting and RT-PCR were used to monitor the regulation of GSDME by Cordycepin (CD) in cancer cell lines. We revealed that GSDME expression is significantly upregulated in eight cancers (ACC, DLBC, GBM, HNSC, LGG, PAAD, SKCM, and THYM) and significantly downregulated in seven cancers (COAD, KICH, LAML, OV, READ, UCES, and UCS). The overall survival was longer only in ACC, but shorter in four cancers, including COAD, KIRC, LIHC, and STAD, when GSDME was highly expressed in cancers compared with the corresponding normal tissues. Moreover, the high expression of GSDME was negatively correlated with the poor prognosis of ACC, while the low expression of GSDME was negatively correlated with the poor prognosis of COAD, suggesting that GSDME might serve as a good prognostic factor in these two cancer types. Accordingly, results indicated that the DNA methylations of those 7 CpG sites constitute a potentially effective signature to distinguish different tumors from adjacent healthy tissues. Gene mutations for GSDME were frequently observed in a variety of tumors, with UCES having the highest frequency. Moreover, CD treatment inhibited GSDME expression in different cancer cell lines, while overexpression of GSDME promoted cell migration and invasion. Thus, we have systematically and successfully clarified the GSDME expression profiles, diagnostic values, and prognostic values in pan-cancers. Targeting GSDME with CD implies therapeutic significance and a mechanism for antitumor roles in some types of cancers via increasing the sensitivity of chemotherapy. Altogether, our study may provide a strategy and biomarker for clinical diagnosis, prognostics, and treatment of cancers by targeting GSDME. [ABSTRACT FROM AUTHOR]

Objective To observe the expression changes of micro RNA-23a(miR-23a) and apoptotic protease-activating factor-1 (APAF-1) in endometrial carcinoma tissues and analyze its clinical significance. Methods 123 specimens of endometrial carcinoma in our hospital from May 2018 to May 2020 were selected as endometrial carcinoma group, and the para cancerous tissue was selected as the normal group. Expression of miR-23a and APAF-1 were examined in endometrial tissues; the relationship between miR-23a and APAF-1 and the clinicopathology of patients and the correlation between the two were analyzed; Kaplan-Meier method was used to analyze the survival of patients with endometrial cancer. Results Compared with the normal group, the expression level of miR-23a in endometrial carcinoma group was significantly increased, the expressions of APAF-1 mRNA and protein decreased significantly (P < 0.05); miR-23a and APAF-1 were significantly correlated with clinical stage, histological differentiation and myometrial invasion (P < 0.05); Pearson analysis showed that miR-23a was negatively correlated with APAF-1 (P < 0.05); Kaplan-Meier curves showed that PFS and OS were significantly higher in the miR-23a low-expression group as well as the APAF-1-positive expression group than in the miR-23a high-expression group and the APAF-1-negative expression group(P < 0.05). Conclusion The expression level of miR-23a is increased and APAF-1 expression is decreased in endometrial carcinoma, both of which correlate with endometrial cancer progression and patient prognosis, are expected to be biomarkers for clinical assessment of disease progression and prognosis in early-stage patients. [ABSTRACT FROM AUTHOR]

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages. While chemotherapy is a common treatment, it often leads to tumor recurrence, necessitating further interventions. In recent years, antibody-drug conjugates (ADCs) have emerged as a valuable tool in targeted cancer therapy. These complex biotherapeutics combine an antibody that specifically targets tumor specific/associated antigen(s) with a high potency anti-cancer drug through a linker, offering a promising approach for ovarian cancer treatment. The identification of molecular targets in various human tumors has paved the way for the development of targeted therapies, with ADCs being at the forefront of this innovation. By delivering cytotoxic agents directly to tumors and metastatic lesions, ADCs show potential in managing chemo-resistant ovarian cancers. Mucins such as MUC16, MUC13, and MUC1 have shown significantly higher expression in ovarian tumors as compared to normal and/or benign samples, thus have become promising targets for ADC generation. While traditional markers are limited by their elevated levels in non-cancerous conditions, mucins offer a new possibility for targeted treatment in ovarian cancer. This review comprehensively described the potential of mucins for the generation of ADC therapy, highlighting their importance in the quest to improve the outcome of ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a leading cause of cancer-related death worldwide. Among various histological types of lung cancer, majority are non-small cell lung cancer (NSCLC) which account for > 80%. Circular RNAs (circRNAs) are widely expressed in various cancers including lung cancer and implicated in tumourigenesis and cancer progression. This study aimed to systematically evaluate the prognostic values of circRNAs in lung cancer. Methods: A systematic literature search was done in PubMed, Embase, and MEDLINE databases to select the eligible studies which reported the association between the expression of circRNAs and overall survival (OS) or disease-free survival (DFS) in histopathologically diagnosed lung cancer patients. The pooled hazard ratio (HR) and 95% confidence interval (CI) were assessed to determine the prognostic significance of circRNAs. Results: A total of 43 studies were eligible for this meta-analysis (MA). 39 different types of circRNAs were reported: 28 showing upregulating and 11 showing downregulating action in lung cancer. High expression of circRNAs with upregulating action in lung cancer was associated with worse prognosis and poor OS (HR 1.93, 95% CI [1.61–2.33], p < 0.00001). High expression of circRNAs with downregulating action in lung cancer was associated with favorable OS and prognosis (HR 0.73, 95% CI [0.58–0.94], p = 0.01). However, there was no statistically significant association between high and low expression of both upregulating and downregulating circRNAs and DFS (HR 1.44, 95% CI [0.92–2.24], p = 0.11). Conclusions: This MA confirmed the pivotal role of circRNAs as important prognostic biomarkers for lung cancer, especially NSCLC. High expression of upregulating circRNAs is associated with poor prognosis; however, high expression of downregulating circRNAs is associated with favorable prognosis. Therefore, downregulatory action of circRNAs should be considered a promising treatment in the management of lung cancer, especially NSCLC. [ABSTRACT FROM AUTHOR]

Background: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. Methods: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. Results: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). Conclusions: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more. [ABSTRACT FROM AUTHOR]

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC. Locally advanced hypopharyngeal squamous cell carcinoma is an aggressive form of head and neck cancer with a poor prognosis. Here, the authors report the safety and efficacy of induction camrelizumab (anti-PD-1) and chemotherapy for the treatment of locally advanced hypopharyngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME. [ABSTRACT FROM AUTHOR]

Background: The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods: We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results: Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions: The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings. [ABSTRACT FROM AUTHOR]