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PurposeTo evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa).MethodsA total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (β) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, β, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann–Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa.ResultsADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while β showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761).ConclusionThe CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.

BackgroundRhabdomyosarcoma of the bladder is an infrequent neoplastic condition characterized by a pronounced malignant situation with challenges in treatment due to the lack of standardized guidelines and large-scale of clinical studies. The patient in this case is tested TP53 mutation that may provide new diagnostic and therapeutic options.Case presentationHere, we reported a 34-year-old male who received bladder tumor resection, and diagnosed as bladder rhabdomyosarcoma with TP53 mutation after the pathology test. This patient underwent 6 rounds of chemotherapy. However, the pelvic tumor recurred 11 months after the first surgery. So, the patient accepted the pelvic tumor resection. Only 3 months after the surgical intervention, the patient underwent abdominal massive metastasis and ultimately succumbed to the illness six months following the second surgery. The course of the illness was 22 months.ConclusionBladder rhabdomyosarcoma is a disease with an extremely poor prognosis. Genetic testing holds significant value in the diagnosis and treatment. Perhaps targeted therapy against TP53 is potential valuable for such rare diseases.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Extramammary Paget disease (EMPD) is a rare cutaneous intraepithelial adenocarcinoma, which is mostly distributed in areas with sweat gland cells and mainly occurs in the anogenital skin of women. The male genital tract involvement is extremely rare and often occurs with other malignant tumors. Paget’s disease in the scrotum with sweat gland carcinoma is even rarer. In the first report of scrotal endocrine sweat gland carcinoma associated with Paget disease by Saidi et al. in 1997, no more than 50 cases have been reported in the relevant research worldwide. Early EMPD combined with sweat gland carcinoma is mainly surgical treatment, and there is no standard treatment plan for advanced EMPD with sweat gland carcinoma. Previous article has reported that chemotherapy such as paclitaxel, fluorouracil, platinum, and vinblastine and molecular targeted therapy based on the genetic test results of patients have certain efficacy. Here, we report a 79-year-old male case diagnosed with human epidermal growth factor receptor 2 (HER-2) overexpression, which was effectively controlled by chemotherapy and anti–HER-2 treatment such as pyrotinib.

The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R “Bibliometrix” package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis.

The tumor control probability (TCP) model has been used for estimating the response of the radiation (photon) therapy for a given treatment dose (distribution). In Taiwan, boron neutron capture therapy (BNCT) is still at the stage of the clinical trials without standard dose prescription. In this study, universal survival curve (USC) model was selected as the TCP model for BNCT. The tumor response and dose distribution from protocol I of the clinical trial of the recurrent head and neck (H&N) cancer conducted by Taipei Veterans General Hospital and National Tsing Hua University were used to verify the TCP model established in this study. The results showed that, using the USC model as a biological model of dose conversion, the TCP calculated by the generalized Equivalent Uniform Dose (gEUD)–based TCP model can be used to well correlate the relationship between the tumor response and dose distribution of the patients of recurrent H&N cancer. The result shows that 25% and 60% of TCP correspond to partial response and complete response of H&N cancer, respectively. This study also indicated that, when BNCT was used to treat recurrent H&N cancer, the minimum dose was an important factor on the efficacy of the treatment. Minimum dose of 18 Gy-w corresponds to at least 60% of TCP.

Background and AimWith the increasing burden of colorectal cancer (CRC), the practice of colonoscopy is gaining attention worldwide. However, it exhibits distinct trends between developing and developed countries. This study aims to explore its development and identify influencing factors in China.MethodsThe Chinese Digestive Endoscopy Censuses were conducted twice in mainland China under the supervision of health authorities. Information regarding the practice of colonoscopy was collected through a structured online questionnaire. The authenticity of the data was evaluated through logical tests, and a random selection of endoscopic reports underwent manual validation by Quality Control Centers. Potential factors associated with colonoscopy were analyzed using real-world information.ResultsFrom 2012 to 2019, the number of hospitals that performed colonoscopy increased from 3,210 to 6,325 (1.97-fold), and the volume increased from 5.83 to 12.92 million (2.21-fold). The utilization rate rose from 436.0 to 914.8 per 100,000 inhabitants (2.10-fold). However, there was an exacerbation of regional inequality in the adequacy of colonoscopy. Regions with higher incidence of CRC, higher gross domestic product per capita, more average numbers of endoscopists and tertiary hospitals tended to provide more accessible colonoscopy (P

BackgroundTo explore the mechanism of OIP5-AS1/CD147/TRPM7 axis to gastric cancer (GC) metastasis.MethodsBioinformatic analysis was performed to pick up the candidate genes associated with regulation GC metastasis. Using GC cell lines, AGS and MKN-45 as research objects, identify the effect of candidate genes on GC metastasis, judge cell proliferation status by MTT assay and cell clone number, and detect cell migration by Transwell and Wound-healing assay. The molecular mechanism of CD147/OIP5/TRPM7 axis regulating GC metastasis was further explored by RNA sequencing. The key signaling pathways were subsequently verified by flow cytometry and WB.ResultsBioinformatic analysis suggested OIP5-AS1/CD147/TRPM7 axis may be involving in GC metastasis. The RNA interference experiment proved that after gene interference, the proliferation ability of GC cells decreased significantly (P

BackgroundThe impact of anticancer therapy and related clinical factors on the severity of COVID-19 in cancer patients during the Omicron pandemic has not been established. The recent outbreak in China caused predominantly by the BA.5.2 and BF.7 strains of Omicron provided us with the opportunity to observe objectively the impact of this strain in oncology patients. We initiated this two–center retrospective study in China to determine the impact of anti-cancer treatment, other clinical factors, and cancer characteristics on COVID-19 severity in cancer patients infected with coronavirus during the SARS-CoV-2 Omicron variant pandemic in China.MethodsWe retrospectively included 554 cancer patients infected with COVID-19 from two medical centers. Data on their anticancer treatment prior to COVID-19 infection and general clinical characteristics (sex, age, past medical history, etc.) were collected. Univariate statistical analysis was performed to identify the factors associated with the severity of COVID-19.ResultsAmong 554 cancer patients infected with COVID-19, there were 15 (2.7%) severe/critical cases, 86 (15.5%) cases with medium severity, and 453 (81.8%) cases with mild severity. Univariate analysis revealed that advanced age, male sex, worse ECOG score, unvaccinated status, and previous liver, kidney, and brain diseases were associated with more severe COVID-19. However, recent antitumor therapy, including cytotoxic chemotherapy within two weeks did not have a significant correlation with the severity of COVID-19 caused by the Omicron variant.ConclusionThe severity of COVID-19 caused by the Omicron variant is not exacerbated by recent anticancer therapy in cancer patients. Therefore, anticancer therapy should not be discontinued in such cases, especially those with mild severity.

BackgroundPrimary small cell neuroendocrine carcinomas of the cervix and endometrium are rare gynecological malignancies with limited treatment options. This study aimed to improve the understanding of the carcinogenesis process and identify potential therapeutic targets for these two tumor types by constructing the mutational landscape at the whole exome level.MethodsPrimary tumor tissues and their matched blood samples were obtained from 10 patients with small cell cervical neuroendocrine carcinoma (NECC) and five patients with small cell endometrial neuroendocrine carcinoma (NECE). Whole exome sequencing was performed to construct the somatic mutation profiles. Mutational signature and recurrent mutated gene analysis were used to identify tumor subtypes and common carcinogenesis processes.ResultsBased on the burden of different mutational signatures, the NECCs in this work can be divided into two subtypes, including the mismatch repair deficiency like (dMMR-like) type (4/10) and the high spontaneous deamination type (6/10). Components of the PI3K/AKT signaling and RAS signaling were exclusively mutated in these two subtypes, respectively. The integration of human papillomavirus made a limited contribution to tumorigenesis in NECC (20%). The dysfunction of the mismatch repair system and microsatellite instability are the major features of NECE. PI3K/AKT, JAK/STAT signaling, and chromatin remodeling activity were the common mutated pathways in NECE. PIK3CA, WNK2, and KMT2B underwent mutations in both the dMMR-like subtype of NECC (50% – 75%) and in NECE (60% – 80%) specimens, while exhibiting infrequent mutational occurrences in publicly available data pertaining to neuroendocrine carcinomas of the lung or bladder (< 10%).ConclusionWe identified the two subtypes of NECC with distinct mutated pathways and potential therapy targets. The dMMR-like type NECC and NECE may share a similar carcinogenesis process that include dysfunction of PI3K/AKT signaling, cell cycle, antiapoptotic processes, and chromatin remodeling activity.

BackgroundPrevious epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs.MethodsThe current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.ResultsDuring follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65–0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results.ConclusionIn the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations.

IntroductionAccurate delineation of tumor targets is crucial for stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). This study aims to develop a deep learning-based segmentation approach to accurately and efficiently delineate NSCLC targets using diagnostic PET-CT and SBRT planning CT (pCT).MethodsThe diagnostic PET was registered to pCT using the transform matrix from registering diagnostic CT to the pCT. We proposed a 3D-UNet-based segmentation method to segment NSCLC tumor targets on dual-modality PET-pCT images. This network contained squeeze-and-excitation and Residual blocks in each convolutional block to perform dynamic channel-wise feature recalibration. Furthermore, up-sampling paths were added to supplement low-resolution features to the model and also to compute the overall loss function. The dice similarity coefficient (DSC), precision, recall, and the average symmetric surface distances were used to assess the performance of the proposed approach on 86 pairs of diagnostic PET and pCT images. The proposed model using dual-modality images was compared with both conventional 3D-UNet architecture and single-modality image input.ResultsThe average DSC of the proposed model with both PET and pCT images was 0.844, compared to 0.795 and 0.827, when using 3D-UNet and nnUnet. It also outperformed using either pCT or PET alone with the same network, which had DSC of 0.823 and 0.732, respectively.DiscussionTherefore, our proposed segmentation approach is able to outperform the current 3D-UNet network with diagnostic PET and pCT images. The integration of two image modalities helps improve segmentation accuracy.

Pleckstrin homologous domain leucine-rich repeating protein phosphatases (PHLPPs) were originally identified as protein kinase B (Akt) kinase hydrophobic motif specific phosphatases to maintain the cellular homeostasis. With the continuous expansion of PHLPPs research, imbalanced-PHLPPs were mainly found as a tumor suppressor gene of a variety of solid tumors. In this review, we simply described the history and structures of PHLPPs and summarized the recent achievements in emerging roles of PHLPPs in lung cancer by 1) the signaling pathways affected by PHLPPs including Phosphoinositide 3-kinase (PI3K)/AKT, RAS/RAF/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and Protein kinase C (PKC) signaling cascades. 2) function of PHLPPs regulatory factor USP46 and miR-190/miR-215, 3) the potential roles of PHLPPs in disease prognosis, Epidermal growth factor receptors (EGFR)- tyrosine kinase inhibitor (TKI) resistance and DNA damage, 4) and the possible function of PHLPPs in radiotherapy, ferroptosis and inflammation response. Therefore, PHLPPs can be considered as either biomarker or prognostic marker for lung cancer treatment.

BackgroundThis study evaluates the diagnostic accuracy of ultrasound-guided fine needle aspiration (US-FNA) and core needle biopsy (US-CNB) for detecting axillary lymph nodes in women with breast cancer.MethodsEligible studies and pertinent literature resources were identified in Cochrane, PubMed, Embase, CNKI, VIP, and Wanfang databases using subject-specific keywords. Study outcomes were tested for heterogeneity, and meta-analyses were performed to estimate sensitivity, specificity, and diagnostic odds ratios (DORs). The summary receiver operating characteristic (SROC) curve analysis was also performed.ResultsA total of 22 studies involving 3,548 patients were included to evaluate the diagnostic accuracy of US-FNA and 11 studies involving 758 patients were included to evaluate the diagnostic accuracy of US-CNB in identifying axillary lymph nodes in women with breast cancer. The accuracy of US-FNA in identifying suspicious axillary lymph nodes was as follows: overall sensitivity, 79% (95% CI: 73%–84%); global specificity, 96% (95% CI: 92%–98%); overall positive likelihood ratio, 18.55 (95% CI: 10.53–32.69); overall negative likelihood ratio, 0.22 (95% CI: 0.17–0.28); DOR, 71.68 (95% CI: 37.19–138.12); and the area under the SROC curve, 0.94 (95% CI: 0.92–0.96). The accuracy of US-CNB in identifying suspicious axillary lymph nodes was as follows: overall sensitivity, 85% (95% CI: 81%–89%); global specificity, 93% (95% CI: 87%–96%); overall positive likelihood ratio, 11.88 (95% CI: 6.56–21.50); overall negative likelihood ratio, 0.16 (95% CI: 0.12–0.21); overall DOR, 66.83 (95% CI: 33.28–134.21), and the area under SROC curve 0.96 (95% CI: 0.94–0.97).ConclusionsThe results indicate that both US-FNA and US-CNB have high accuracy for suspicious axillary lymph nodes.

BackgroundRenal clear cell carcinoma (RCC) has negative prognosis and high mortality due to its early diagnosis difficulty and early metastasis. Although previous studies have confirmed the negative progression of RCC is closely related to M2 macrophages in tumor-associated macrophages (TAMs), the specific mechanism is still unknownMethodsWe used immunofluorescence labeling and flow cytometry to detect the proportion of M2 macrophages in RCC tissues. And bioinformatics technique was used to obtain 9 M2 macrophage-related model genes, including SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12. Using these genes, model formulas are constructed to devide samples into high and low risk groups, and then the overall survival (OS), progression-free survival (PFS) and Gene set enrichment analysis (GSEA) of the high and low risk groups were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of model genes between normal kidney tissue and RCC tissue, as well as between HK-2 cell and 786-O cell. Besides, we induced the M2 differentiation of THP-1 cell, and then co-cultured with the RCC cell 786-O in transwell to observe what effect M2 macrophages will cause on the invasion, migration and the expression of model genes of RCC.ResultsOur study demonstrated M2 macrophages in RCC was about 2 folds that of normal renal tissue (P

BackgroundThere are a variety of treatment options for recurrent platinum-resistant ovarian cancer, and the optimal specific treatment still remains to be determined. Therefore, this Bayesian network meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-resistant ovarian cancer.MethodsPubmed, Cochrane, Embase, and Web of Science were searched for articles published until 15 June 2022. The outcome measures for this meta-analysis were overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of Grade 3-4. The Cochrane assessment tool for risk of bias was used to evaluate the risk of bias of the included original studies. The Bayesian network meta-analysis was conducted. This study was registered on PROSPERO (CRD42022347273).ResultsOur systematic review included 11 RCTs involving 1871 patients and 11 treatments other than chemotherapy. The results of meta-analysis showed that the overall survival (OS) was the highest in adavosertib + gemcitabine compared with conventional chemotherapy, (HR=0.56,95%CI:0.35-0.91), followed by sorafenib + topotecan (HR=0.65, 95%CI:0.45-0.93). In addition, Adavosertib + Gemcitabine regimen had the highest PFS (HR=0.55,95%CI:0.34-0.88), followed by Bevacizumab + Gemcitabine regimen (HR=0.48,95%CI:0.38-0.60) and the immunotherapy of nivolumab was the safest (HR=0.164,95%CI:0.312-0.871) with least adverse events of Grades 3-4.ConclusionsThe results of this study indicated that Adavosertib (WEE1 kinase-inhibitor) + gemcitabine regimen and Bevacizumab + Gemcitabine regimen would be significantly beneficial to patients with recurrent platinum-resistant ovarian cancer, and could be preferred for recurrent platinum-resistant ovarian cancer. The immunotherapeutic agent, Nivolumab, is of considerable safety, with a low risk for grade-III or IV adverse events. Its safety is comparable to Adavosertib + gemcitabine regimen. Pazopanib + Paclitaxel (weekly regimen), Sorafenib + Topotecan/Nivolumab could be selected if there are contraindications of the above strategies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022347273.

BackgroundThe purpose of this study is to investigate the predictive significance of (platelet × albumin)/lymphocyte ratio (PALR) for lymph node metastasis (LNM) in patients with clinically node-negative colon cancer (cN0 CC).MethodsData from 800 patients with primary CC who underwent radical surgery between March 2016 and June 2021 were reviewed. The non-linear relationship between PALR and the risk of LNM was explored using a restricted cubic spline (RCS) function while a receiver operating characteristic (ROC) curve was developed to determine the predictive value of PALR. Patients were categorized into high- and low-PALR cohorts according to the optimum cut-off values derived from Youden’s index. Univariate and multivariate logistic regression analyses were used to identify the independent indicators of LNM. Sensitivity analysis was performed to repeat the main analyses with the quartile of PALR.ResultsA total of eligible 269 patients with primary cN0 CC were retrospectively selected. The value of the area under the ROC curve for PALR for predicting LNM was 0.607. RCS visualized the uptrend linear relationship between PALR and the risk of LNM (p-value for non-linearity > 0.05). PALR (odds ratio = 2.118, 95% confidence interval, 1.182-3.786, p = 0.011) was identified as an independent predictor of LNM in patients with cN0 CC. A nomogram incorporating PALR and other independent predictors was constructed with an internally validated concordance index of 0.637. The results of calibration plots and decision curve analysis supported a good performance ability and the sensitivity analysis further confirmed the robustness of our findings.ConclusionPALR has promising clinical applications for predicting LNM in patients with cN0 CC.

Chronic lymphocytic leukemia (CLL) is a subtype of mature B-cell proliferative neoplasms characterized by abnormally increasing lymphocytes in circulation. The diagnosis of CLL is usually established on peripheral blood analysis and typical flow cytometric immunophenotype rather than biopsy. In particular, the high RMH (Royal Marsden Hospital Scoring System for CLL) score of immunophenotype has a highly sensitive weight for diagnostic value. However, immunophenotyping by flow cytometry may also be misleading in specific clinical situations. Here, we report a case on admission with lymphadenopathy and lymphocytosis, misdiagnosed as chronic lymphocytic leukemia by flow cytometry initially but finally confirmed as follicular lymphoma (FL) in the leukemic phase via lymph node biopsy. Since FL in the leukemic phase is uncommon at the time of diagnosis and indicates a poorer prognosis of FL, such misdiagnosis is worthy of attention. It is also thought-provoking that there had been conflicts between immunophenotype of bone marrow and immunohistochemistry of lymph node. Our case report aims to remind clinicians’ awareness that the immunophenotyping by flow cytometric analysis needs to be interpreted with caution especially when the results cannot account for all of clinical features, and it is significant to make the right decision about when to conduct further examination including lymph node biopsy for avoiding misdiagnosis.

Liver cancer is a common malignancy of the digestive system. Hepatocellular carcinoma (HCC) accounts for the most majority of these tumors and it has brought a heavy medical burden to underdeveloped countries and regions. Many factors affect the prognosis of HCC patients, however, there is no specific statistical model to predict the survival time of clinical patients. This study derived a risk factor signature of HCC and reliable clinical prediction model by statistically analyzing The Surveillance, Epidemiology, and End Results (SEER) database patient information using an open source package in the python environment.

Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumour and was newly named in 2019. This study reported a case of a 30-year-old female patient with a left renal tumour without any clinical symptoms and whose CT scan of her left kidney showed a mass of 2.6 cm×2.3 cm, which was considered to be renal clear cell carcinoma. Laparoscopic partial nephrectomy was performed, and histopathology and immunohistochemistry confirmed papillary renal neoplasm with reverse polarity, which had unique clinicopathological features, immunophenotype, KRAS gene mutation and relatively indolent biological behaviour. As newly diagnosed cases, rigorous and regular follow-up is necessary. In addition, a literature review was performed from 1978 to 2022, and 97 cases of papillary renal neoplasms with reverse polarity were identified and analysed.

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.

ObjectiveWe investigated the effects of different treatment modalities and clinical stage for hypopharyngeal carcinoma (HPC) patients.MethodsBetween February 2004 and December 2012, 167 HPC patients were reviewed. We calculated overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS), regional failure-free survival (RFFS), and distant metastasis failure-free survival (DMFFS) using the Kaplan–Meier method and compared various survival outcomes between definitive chemoradiotherapy (CRT) and surgery-based therapy (SBT).ResultsThere were no significant differences in baseline characteristics between SBT (n = 102) and definitive CRT (n = 65) groups. The 5-year rates of OS (59.7% vs. 24.0%, p < 0.0001) and PFS (49.9% vs. 22.6%, p = 0.0002) were significantly better in patients who received SBT than in those who received definitive CRT. The SBT group also obtained better LFFS (p < 0.0001), RFFS (p = 0.0479), and DMFFS (p = 0.0110). We did similar analyses by different T-classification (T1–2, T3, and T4) and found that SBT had better OS (p < 0.0001 and p = 0.0020), PFS (p < 0.0001 and p = 0.0513), LFFS (p = 0.0002 and p = 0.0075), RFFS (p = 0.1949 and p = 0.0826), and DMFFS (p = 0.0248 and p = 0.0436) in the T4 and T1–2 subgroups but similar OS (p = 0.9598), PFS (p = 0.5052), RFFS (p = 0.9648), and DMFFS (p = 0.8239) in T3 patients. Analyses by different overall stages revealed no differences between definitive CRT and SBT for stage III patients but significantly better results for stage IV patients who received SBT.ConclusionsSBT can obtain significant survival benefits when compared with definitive CRT for the whole cohort of patients. Definitive CRT has similar survival outcomes compared with SBT only for T3 tumors or overall stage III disease.

Esophageal cancer-related gene-4 (ECRG4), a 148-amino acid propertied and new tumor suppressor, is initially cloned from the normal esophageal epithelium. ECRG4 was found to be expressed not only in esophageal tissues but also in cardiomyocytes. Previous studies demonstrated that ECRG4 is constitutively expressed in esophageal epithelial cells, and its degree of downregulation is directly proportional to prognosis in patients with esophageal cancer. In the heart, ECRG4 shows greater expression in the atria than in the ventricles, which accounts for its heterogeneity. Downregulation of ECRG4 expression level correlates with esophageal cancer, as well as myocardial injuries and arrhythmias. As a result, this review summarizes the possible susceptibility gene, ECRG4 and its associated molecular mechanisms in cancer patients with atrial fibrillation and myocardial injury. The review begins by describing ECRG4’s biological background, discusses its expression in the cardiovascular system, lists the clinical and animal research related to the downregulation of ECRG4 in atrial fibrillation, and focuses on its potential role in atrial fibrillation. Downregulation of ECRG4 may increase the risk of atrial fibrillation by affecting ion channels, MMPs expression and inflammatory response. We will then discuss how ECRG4 can be used in the treatment of tumors and arrhythmias, and provide a novel possible strategy to reduce the occurrence of perioperative cardiovascular adverse events in patients with tumors such as esophageal cancer and gastric cancer.

BackgroundThe prognostic model based on oxidative stress for lung adenocarcinoma (LUAD) remains unclear.MethodsThe information of LUAD patients were acquired from TCGA dataset. We also collected two external datasets from GEO for verification. Oxidative stress-related genes (ORGs) were extracted from Genecards. We performed machine learning algorithms, including Univariate Cox regression, Random Survival Forest, and Least Absolute Shrinkage and Selection Operator (Lasso) analyses on the ORGs to build the OS-score and OS-signature. We drew the Kaplan-Meier and time-dependent receiver operating characteristic curve (ROC) to evaluate the efficacy of the OS-signature in predicting the prognosis of LUAD. We used GISTIC 2.0 and maftool algorithms to explore Genomic mutation of OS-signature. To analyze characteristic of tumor infiltrating immune cells, ESTIMATE, TIMER2.0, MCPcounter and ssGSEA algorithms were applied, thus evaluating the immunotherapeutic strategies. Chemotherapeutics sensitivity analysis was based on pRRophetic package. Finally, PCR assays was also used to detect the expression values of related genes in the OS-signature in cell lines.ResultsTen ORGs with prognostic value and the OS-signature containing three prognostic ORGs were identified. The significantly better prognosis of LUAD patients was observed in LUAD patients. The efficiency and accuracy of OS-signature in predicting prognosis for LUAD patients was confirmed by survival ROC curves and two external validation data sets. It was clearly observed that patients with high OS-scores had lower immunomodulators levels (with a few exceptions), stromal score, immune score, ESTIMATE score and infiltrating immune cell populations. On the contrary, patients with higher OS-scores were more likely to have higher tumor purity. PCR assays showed that, MRPL44 and CYCS were significantly higher expressed in LUAD cell lines, while CAT was significantly lower expressed.ConclusionThe novel oxidative stress-related model we identified could be used for prognosis and treatment prediction in lung adenocarcinoma.

BackgroundCuproptosis, a unique kind of cell death, has implications for cancer therapy, particularly lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) have been demonstrated to influence cancer cell activity by binding to a wide variety of targets, including DNA, RNA, and proteins.MethodsCuproptosis-related lncRNAs (CRlncRNAs) were utilized to build a risk model that classified patients into high-and low-risk groups. Based on the CRlncRNAs in the model, Consensus clustering analysis was used to classify LUAD patients into different subtypes. Next, we explored the differences in overall survival (OS), the tumor immune microenvironment (TIME), and the mutation landscape between different risk groups and molecular subtypes. Finally, the functions of LINC00592 were verified through in vitro experiments.ResultsPatients in various risk categories and molecular subtypes showed statistically significant variations in terms of OS, immune cell infiltration, pathway activity, and mutation patterns. Cell experiments revealed that LINC00592 knockdown significantly reduced LUAD cell proliferation, invasion, and migration ability.ConclusionThe development of a trustworthy prediction model based on CRlncRNAs may significantly aid in the assessment of patient prognosis, molecular features, and therapeutic modalities and may eventually be used in clinical applications.

BackgroundProgrammed death ligand 1 (PD-L1) and tumor mutation burden (TMB) have been developed as biomarkers for the treatment of immune checkpoint inhibitors (ICIs). However, some patients who are TMB-high or PD-L1-high remained resistant to ICIs therapy. Therefore, a more clinically applicable and effective model for predicting the efficacy of ICIs is urgently needed.MethodsIn this study, genomic data for 466 patients with melanoma treated with ICIs from seven independent cohorts were collected and used as training and validation cohorts (training cohort n = 300, validation cohort1 n = 61, validation cohort2 n = 105). Ten machine learning classifiers, including Random Forest classifier, Stochastic Gradient Descent (SGD) classifier and Linear Support Vector Classifier (SVC), were subsequently evaluated. ResultsThe Linear SVC with a 186-gene mutation-based set was screened to construct the durable clinical benefit (DCB) model. Patients predicted to have DCB (pDCB) were associated with a better response to the treatment of ICIs in the validation cohort1 (AUC=0.838) and cohort2 (AUC=0.993). Compared with TMB and other reported genetic mutation-based signatures, the DCB model showed greater predictive power. Furthermore, we explored the genomic features in determining the benefits of ICIs treatment and found that patients with pDCB were associated with higher tumor immunogenicity. ConclusionThe DCB model constructed in this study can effectively predict the efficacy of ICIs treatment in patients with melanoma, which will be helpful for clinical decision-making.

IntroductionIt has been believed that breast-conserving therapy (lumpectomy plus adjuvant radiation, Lum + RT) and mastectomy without radiation (Mast + NoRT) have equivalent survival outcomes. However, there is a need to re-evaluate the role of lumpectomy plus adjuvant radiation due to changed breast cancer management over time. This study aimed to conduct a population-based study that compare long-term oncologic survival outcomes after Lum + RT vs Mast + NoRT.MethodsThe Surveillance, Epidemiology and End Results database was used to identify female breast cancer patients with a primary localized breast cancer diagnosis from 1988 to 2018. The standardized incidence/mortality ratio (SIR/SMR) for breast cancer recurrence (BCR) and breast cancer-specific death (BSD) was estimated by the SEER*Stat program. Cumulative incidences of BCR and BSD were assessed using Gray’s method. We evaluated the effects of Lum + RT vs. Mast + NoRT on breast cancer recurrence-free survival (BRFS) and breast cancer-specific survival (BCSS). Fine-Gray competing risk model analyses, propensity score-adjusted Kaplan-Meier analyses and Cox proportional hazards model analyses were applied.ResultsA total of 205,788 women were included in the study. Patients who underwent Lum + RT had higher SIR of BCR (4.14 [95% confidence interval, CI: 3.94-4.34] vs. 1.11 [95% CI: 1.07-1.14]) and lower SMR (9.89 [95% CI: 9.71-10.08] vs. 17.07 [95% CI: 16.82-17.33]) than patients who underwent Mast + NoRT. Lum + RT was associated with higher competing risk of BCR (adjusted hazard ratio [HR]: 1.996, 95% CI: 1.925-2.069, p < 0.001) and lower competing risk of BSD when compared to Mast + RT (adjusted HR: 0.584, 95% CI: 0.572-0.597, p < 0.001). Multivariate Cox regression analysis revealed similar results (adjusted HR after PSW for BRFS: 1.792, 95% CI 1.716-1.871, p < 0.001; adjusted HR after PSW for BCSS: 0.706, 95% CI 0.688-0.725, p < 0.001). These findings persisted in the sensitivity and subgroup analyses.DiscussionThe present study further confirmed superior long-term survival with lumpectomy plus adjuvant radiation over mastectomy independent of patient characteristics including age, race, time period, historic subtype, tumor size, historic grade and stage, indicating that this benefit may result from the treatment itself.

Cancer is a major medical problem worldwide. Due to its high heterogeneity, the use of the same drugs or surgical methods in patients with the same tumor may have different curative effects, leading to the need for more accurate treatment methods for tumors and personalized treatments for patients. The precise treatment of tumors is essential, which renders obtaining an in-depth understanding of the changes that tumors undergo urgent, including changes in their genes, proteins and cancer cell phenotypes, in order to develop targeted treatment strategies for patients. Artificial intelligence (AI) based on big data can extract the hidden patterns, important information, and corresponding knowledge behind the enormous amount of data. For example, the ML and deep learning of subsets of AI can be used to mine the deep-level information in genomics, transcriptomics, proteomics, radiomics, digital pathological images, and other data, which can make clinicians synthetically and comprehensively understand tumors. In addition, AI can find new biomarkers from data to assist tumor screening, detection, diagnosis, treatment and prognosis prediction, so as to providing the best treatment for individual patients and improving their clinical outcomes.

IntroductionTo develop and validate a radiogenomics model for predicting axillary lymph node metastasis (ALNM) in breast cancer compared to a genomics and radiomics model.MethodsThis retrospective study integrated transcriptomic data from The Cancer Genome Atlas with matched MRI data from The Cancer Imaging Archive for the same set of 111 patients with breast cancer, which were used as the training and testing groups. Fifteen patients from one hospital were enrolled as the external validation group. Radiomics features were extracted from dynamic contrast-enhanced (DCE)-MRI of breast cancer, and genomics features were derived from differentially expressed gene analysis of transcriptome data. Boruta was used for genomics and radiomics data dimension reduction and feature selection. Logistic regression was applied to develop genomics, radiomics, and radiogenomics models to predict ALNM. The performance of the three models was assessed by receiver operating characteristic curves and compared by the Delong test.ResultsThe genomics model was established by nine genomics features, and the radiomics model was established by three radiomics features. The two models showed good discrimination performance in predicting ALNM in breast cancer, with areas under the curves (AUCs) of 0.80, 0.67, and 0.52 for the genomics model and 0.72, 0.68, and 0.71 for the radiomics model in the training, testing and external validation groups, respectively. The radiogenomics model integrated with five genomics features and three radiomics features had a better performance, with AUCs of 0.84, 0.75, and 0.82 in the three groups, respectively, which was higher than the AUC of the radiomics model in the training group and the genomics model in the external validation group (both P < 0.05).ConclusionThe radiogenomics model combining radiomics features and genomics features improved the performance to predict ALNM in breast cancer.

BackgroundAs a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study.MethodsThe Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer.ResultsFrom 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer).ConclusionResearch on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial–mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.

Background and aimThe prevalence of small submucosal gastric tumors is rising. Despite the fact that high success rate of endoscopic resection of small submucosal gastric tumors originating from the muscularis propria has been reported, the procedure is technically challenging and has a high rate of complications. In this study, we investigated the efficacy and feasibility of a novel snare-assisted endoscopic resection technique for small submucosal gastric tumors.Patients and methodsThis is a single-center consecutive study of 50 patients who were diagnosed with small submucosal gastric tumors originating from the muscularis propria and who subsequently underwent snare-assisted endoscopic resection between January 2019 and January 2021 at our hospital. Data on the demographic characteristics, procedural success rate, complications, recurrence rate, and histopathology of the resected specimen were collected and analyzed retrospectively.ResultsThe majority of the patient’s population was male (66%) with the mean age of 48.4 ± 9 years (range, 20–70 years). The mean size of the tumor confirmed by endoscopic ultrasonography was 6.4 ± 1.6 mm (range, 3.1–9.8 mm). All the tumors were resected successfully using snare-assisted endoscopic resection technique. The mean procedure time was 22.8 ± 9.6 (range, 15–35 min). The technical (performed the procedure successfully without converting to surgery) and clinical (the patient fully recovered after the procedure without experiencing any complications) success rate of the procedure was 100%. Eighteen (24%) patients had very small amount of mucosal damage, and wound closure was not needed in these patients. During 6–24 months of follow-up, no recurrence or metastasis occurred. No adverse event was noted during the follow-up time.ConclusionThe novel approach of snare-assisted endoscopic resection is simple, feasible, and effective for tumors with small size and originating from the gastric muscularis propria. In addition, it offers a better alternative therapy for the complete resection of small submucosal gastric tumors. Its advantages compared with traditional endoscopic approaches such as endoscopic submucosal resection and endoscopic submucosal dissection include shorter procedure times, lesser cost, and a lower rate of complications (perforation, bleeding, and infection).

BackgroundCholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelial cells that no obvious clinical symptoms and specific clinical manifestations are shown in the early stage of CCA.MethodsPropensity score matching (PSM) is a quasi-experimental method in which this study used. Patients were enrolled from Department of General surgery, First Affiliated Hospital of Jinzhou Medical University from March 1, 2010, to December 30, 2019. Totally 170 patients with CCA were enrolled in this study.ResultsWe performed a 1:2 PSM study and found that patients with losartan group showed both comparable median OS (overall survival) and TTR (time to recurrence) to those in the patients without losartan group before PSM. However, after matching, patients with losartan group showed favorable median OS and TTR than those in the patients without losartan group. Then we performed Cox proportional hazards models and found that patients with losartan was an independent factor after multivariable analysis for patients with CCA. Furtherly, we sequenced serial cfDNA were performed in 10 patients with losartan and 9 patients without losartan who received adjuvant chemotherapy after tumor resection. These results showed that the treatment of losartan was related with tumor microenvironment and could be potentially useful to combine the immunotherapy for patients with CCA.ConclusionIn conclusion, this study demonstrated that the treatment of losartan could increase the efficacy of adjuvant chemotherapy and identified as an independent survival predictor for patients with CCA. Moreover, losartan could be potentially useful to combine the immunotherapy for patients with CCA.

Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.

BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.

BackgroundHepatocellular carcinoma (HCC) is a high-burden cancer. The molecular mechanism of HCC has not been fully elucidated. Notably, current research has revealed a significant function for long non-coding RNAs (lncRNAs) in the prognosis of patients with HCC. Here, this study aims to construct a regulated lncRNA-mediated ceRNA network and find biological targets for the treatment of HCC.MethodsBased on the RNA expression patterns from the TCGA, we did an analysis to determine which genes were expressed differently between liver tumor tissues and noncancerous tissues. Then, using bioinformatic tools, we built a lncRNA-miRNA-mRNA ceRNA network and used GO and KEGG functional analyses on the DEmRNAs connected to ceRNA networks. The main lncRNAs in the subnetwork were chosen, and we next looked at the relationships between these lncRNAs and the clinical characteristics of patients with HCC. The prognosis-related genes and immune cells were identified using Kaplan-Meier and Cox proportional hazard analyses, and CIBERSORT was utilized to separate the 22 immune cell types. CCK8 assay was performed to measure cell viability in HCC cells after lncRNA HOTTIP modulation.ResultsDifferentially expressed mRNA and lncRNAs in HCC and paracancerous tissues were identified. There are 245 lncRNAs, 126 miRNAs, and 1980 mRNAs that are expressed differently in liver tumour tissues than in noncancerous cells. Function analysis showed that mRNAs in ceRNA network were significantly enriched in G1/S transition of mototiv cell cycle, positive regulation of cell cycle process, hepatocellular carcinoma, and cancer related pathways. CD8 T cells and T follicular helper cells had a favourable link with a 0.65 correlation coefficient. Additionally, there was a strong correlation between Eosinophils, activated NK cells, and B memory cells. Strikingly, depletion of lncRNA HOTTIP inhibited viability of HCC cells. In addition, miR-205 upregulation suppressed viability of HCC cells, while miR-205 downregulation repressed viability of HCC cells. Notably, miR-205 depletion rescued HOTTIP depletion-mediated suppression of cell viability in HCC.ConclusionA ceRNA network was created by examining the lncRNA, miRNA, and mRNA expression profiles of liver tumours from the TCGA database. LncRNA HOTTIP promoted cell viability via inhibition of miR-205 in HCC cells.

BackgroundSystemic immune-inflammation states across the heterogeneous population of brain metastases from lung cancer are very important, especially in the context of complex brain-immune bidirectional communication. Previous studies from our team and others have shown that the L1 cell adhesion molecule (L1CAM) is deeply involved in the aggressive phenotype, immunosuppressive tumor microenvironment (TME), and metastasis during multiple malignancies, which may lead to an unfavorable outcome. However, little is known about the relationship between the L1CAM expression and the systemic immune-inflammation macroenvironment beyond the TME in brain metastases from lung cancer.MethodsTwo cohorts of patients with brain metastases from lung cancer admitted to the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, were studied in the present research. The L1CAM expression in cranial metastatic lesions by immunohistochemistry was explored in patients treated with neurosurgical resection, whereas the L1CAM expression in peripheral blood by ELISA was tested in patients treated with non-surgical antitumor management. Furthermore, based on peripheral blood cell counts in the CBC test, six systemic immune-inflammation biomarkers [neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio] were calculated. Then, the relationship between the L1CAM expression and these systemic immune-inflammation biomarkers was analyzed. In addition, these systemic immune-inflammation biomarkers were also used to compare the systemic immune-inflammation states in two cohorts of patients with brain metastases from lung cancer.ResultsPositive L1CAM expressions in the metastatic brain lesions were accompanied with significantly increased peripheral platelet counts in patients treated with neurosurgical tumor resection (P < 0.05). Similarly, in patients treated with non-surgical antitumor management, L1CAM expressions in the peripheral blood were positively correlated with peripheral platelet counts (P < 0.05). In addition, patients prepared for neurosurgical tumor resection were presented with poorer systemic immune-inflammation states in comparison with the one with non-surgical antitumor management, which was characterized by a significant increase in peripheral neutrophil counts (P < 0.01), SII (P < 0.05), and NLR (P < 0.05) levels.ConclusionThe L1CAM expression in either the metastatic brain lesion or peripheral blood is positively correlated with the peripheral platelet count in patients with brain metastases from lung cancer. In addition, brain metastases that are prepared for neurosurgical tumor resection show poor systemic immune-inflammation states.

BackgroundTo compare the perioperative and short-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) in recurrent hepatocellular carcinoma (rHCC) based on propensity score matching (PSM) to investigate therapeutic safety, efficacy, and value for clinical application.MethodsForty-nine patients with rHCC who underwent surgery at Wenzhou People’s Hospital between January 2017 and March 2022 were retrospectively analyzed and classified into LLR (n=30) and OLR (n=22) cases based on the surgical method. Thirty-eight patients were screened using PSM for data analysis to compare basic clinical characteristics, perioperative outcomes, and postoperative recurrence in both groups.ResultsBefore PSM, the tumour diameter was larger, tumor staging (BCLC staging system), intraoperative blood loss, units of blood transfused, constituent ratio of liver cirrhosis, incidence of MVI and intravascular tumour thrombus and postoperative complication were higher, and duration of hospital stay was significantly longer in the OLR group compared to those in the LLR group (p < 0.05). After PSM, there were no significant differences regarding tumour diameter, MVI incidence, blood transfusion amount or postoperative complication rate in the LLR and OLR groups. The tumor staging, incidence of vascular cancer thrombus, intraoperative blood loss and postoperative duration of hospitalisation were significantly higher in the OLR group than in the LLR group (p

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, μg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.

BackgroundPoor prognosis, resistance to chemotherapy, insensitivity to radiotherapy, and a high prevalence of adverse drug reactions remain urgent issues for breast cancer (BC) patients. Increased knowledge of tumor immunobiology and vaccine development suggests the possibility of cancer vaccination. Here, we investigated potential BC-associated antigens for the development of an anti-BC mRNA vaccine and populations suitable for mRNA vaccination.MethodsGene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). The single-cell sequencing data were obtained from the Single Cell Portal platform. cBioPortal was used to visualize and compare genetic alterations. Correlations between immune cell infiltration and antigen expression were visualized with the Tumor Immune Estimation Resource (TIMER). Immune subtypes were identified by consensus clustering and analysis of immune infiltration. Biomarkers for the assessment of mRNA vaccination suitability were investigated.ResultsThree tumor-associated antigens, CD74, IRF1, and PSME2, that showed overexpression, amplification, and mutation and were linked with prognosis and immune cell infiltration, were identified. Single-cell sequencing analysis showed the expression of the three tumor-associated antigens in different cells of BC. Three immune subtypes were identified among BC patients, with Cluster B patients having a tumor microenvironment conducive to immunotherapy. These subtypes also showed different expression patterns of immune checkpoints, immune cell death-promoting genes, and response to immune checkpoint inhibitor (ICI) therapy. Thus, we identified five biomarkers that could be applied for assessing vaccination suitability and predicted drugs that would be appropriate for patients unsuited for vaccination.ConclusionsOur findings suggest new directions for the development of mRNA vaccines against breast cancer.

Pancreatic adenocarcinoma (PAAD) is one of the most aggressive digestive system tumors in the world, with a low early diagnosis rate and a high mortality. Integrin beta 5 (ITGB5) is demonstrated to be a potent tumor promoter in several carcinomas. However, it is unknown whether ITGB5 participates in the occurrence and development of PAAD. In this study, we confirmed a high expression of ITGB5 in PAAD and its role in promoting invasiveness and transitivity in PAAD. Besides, the knockdown of ITGB5 increased cell sensitivity to radiation by promoting DNA damage repair and the MEK/ERK signaling pathway. Collectively, these results show that ITGB5 plays an essential role in pancreatic cancer growth and survival.

Urothelial carcinomas (UCs) are malignant tumors that arise from the lower and upper urinary tract and are characterized by multiple recurrences. Aristolochic acid (AA) is a potent nephrotoxin and human carcinogen associated with UC. East Asian populations with a high UC prevalence have an unusual genome-wide AA-induced mutational pattern. To address the genomic differences and clonal relatedness between primary and recurrent tumors in the UCs with AA pattern, we investigated the genomic differences and tumor microenvironment (TME) of AA and non-AA UCs. 17 UC patients were recruited, with nine documented AA exposure. Eleven of them showed recurrence. After-surgery tissues of primary and paired recurrent tumors were collected. Capture-based targeted deep sequencing was performed using a commercial panel consisting of 520 cancer-related genes. Tumor-infiltrating lymphocytes (TILs) were identified with an immunofluorescence-based microenvironment analysis panel (MAP). Hierarchical clustering based on the COSMIC signatures confirmed two significant subtypes: AA Sig and non-AA Sig. AA Sig was associated with AA-containing herbal drug intake, recurrence, and higher tumor mutation burden (TMB). The clonal architecture of UCs revealed three types of clonal evolution patterns. Non-AA Sig cohort showed shared clonal origin of primary and recurrent tumors. AA Sig showed heterogeneity and had multiple independent origins. Recurrent tumors as second primary tumors in AA Sig showed immunoreactive TME, indicating a better response with immune checkpoint inhibitor therapy. The AA mutational signature and unique immune profiles are helpful molecular markers to distinguish AA exposure from other carcinogens. These results also provide new insights into the origin of recurrent UCs that could affect treatment strategies.

BackgroundProline metabolism is closely related to the occurrence and development of cancer. Δ1-Pyrroline-5-carboxylate reductase (PYCR) is the last enzyme in proline biosynthesis. As one of the enzyme types, PYCR1 takes part in the whole process of the growth, invasion, and drug resistance of cancer cells. This study investigated PYCR1 expressions in cancers together with their relationship to clinical prognosis.MethodsA thorough database search was performed in PubMed, EMBASE, and Cochrane Library. RevMan5.3 software was used for the statistical analysis.ResultsEight articles were selected, and 728 cancer patients were enrolled. The cancer types include lung, stomach, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. The meta-analysis results showed that the expression of PYCR1 was higher in the clinical stage III–IV group than that in the clinical stage I–II group (OR = 1.67, 95%CI: 1.03–2.71), higher in the lymph node metastasis group than in the non-lymph node metastasis group (OR = 1.57, 95%CI: 1.06–2.33), and higher in the distant metastasis group than in the non-distant metastasis group (OR = 3.46, 95%CI: 1.64–7.29). However, there was no statistical difference in PYCR1 expression between different tumor sizes (OR = 1.50, 95%CI: 0.89–2.53) and degrees of differentiation (OR = 0.82, 95%CI: 0.54–1.24).ConclusionPYCR1 had a high expression in various cancers and was associated with cancer volume and metastasis. The higher the PYCR1 expression was, the poorer the cancer prognosis was. The molecular events and biological processes mediated by PYCR1 might be the underlying mechanisms of metastasis.

The TEMPI syndrome is a novel and rare disease with five distinct clinical features: Telangiectasis, Erythrocytosis, Monoclonal gammopathy, Perinephric fluids collection, and Intrapulmonary shunting. Here, we report three cases of TEMPI syndrome and their treatment response. The three patients were presented to our department with polycythemia, abdominal distension, and dyspnea. On admission, all patients manifested telangiectasis, erythrocytosis, monoclonal gammopathy, and intrapulmonary shunting. Patient 1 and 2 manifested perinephric fluids collection. In addition, all patients had skin pigmentation, patient 1 and 2 had polyserosal effusion, two symptoms that had not been associated with TEMPI syndrome before. The three patients showed various response to plasma cell-directed therapy. We demonstrated their treatment response by measuring erythropoietin, hemoglobin, and M protein levels throughout therapy. This report suggested that TEMPI syndrome is a rare yet treatable disease. The diagnosis and treatment of it remain challenging.

PurposePatients with advanced ovarian cancer often undergo en bloc rectosigmoid resection with total hysterectomy to completely debulk the pelvis. We describe a unique rectosigmoid sparing en bloc pelvic resection technique for fixed ovarian tumors infiltrating the colon wall.MethodsFrom July 2020 to June 2021, 20 patients with advanced epithelial ovarian cancer (EOC) underwent rectosigmoid sparing en bloc pelvic resection successfully at our institution. We summarized our surgical technique and the peri-operative and oncological outcomes.ResultsTwenty cases with bowel infiltration achieved en bloc pelvic resection with rectosigmoid tumorectomy in a centripetal fashion. Only two patients required mucosal repair. None of the patients experienced any complications associated with en bloc resection. No pelvic recurrence occurred within the median follow-up time of 12 months.ConclusionRectosigmoid sparing en bloc pelvic resection may be feasible for select patients with fixed ovarian tumors infiltrating the colon wall.

ObjectiveTo develop and validate a radiomics nomogram that could incorporate clinicopathological characteristics and ultrasound (US)-based radiomics signature to non-invasively predict Ki-67 expression level in patients with breast cancer (BC) preoperatively.MethodsA total of 328 breast lesions from 324 patients with BC who were pathologically confirmed in our hospital from June 2019 to October 2020 were included, and they were divided into high Ki-67 expression level group and low Ki-67 expression level group. Routine US and shear wave elastography (SWE) were performed for each lesion, and the ipsilateral axillary lymph nodes (ALNs) were scanned for abnormal changes. The datasets were randomly divided into training and validation cohorts with a ratio of 7:3. Correlation analysis and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomics features obtained from gray-scale US images of BC patients, and each radiomics score (Rad-score) was calculated. Afterwards, multivariate logistic regression analysis was used to establish a radiomics nomogram based on the radiomics signature and clinicopathological characteristics. The prediction performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA) using the results of immunohistochemistry as the gold standard.ResultsThe radiomics signature, consisted of eight selected radiomics features, achieved a nearly moderate prediction efficacy with AUC of 0.821 (95% CI:0.764-0.880) and 0.713 (95% CI:0.612-0.814) in the training and validation cohorts, respectively. The radiomics nomogram, incorporating maximum diameter of lesions, stiff rim sign, US-reported ALN status, and radiomics signature showed a promising performance for prediction of Ki-67 expression level, with AUC of 0.904 (95% CI:0.860-0.948) and 0.890 (95% CI:0.817-0.964) in the training and validation cohorts, respectively. The calibration curve and DCA indicated promising consistency and clinical applicability.ConclusionThe proposed US-based radiomics nomogram could be used to non-invasively predict Ki-67 expression level in BC patients preoperatively, and to assist clinicians in making reliable clinical decisions.

Pulmonary infections account for a large proportion of life-threatening adverse events that occur after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL); however, data on their influencing risk factors and the effects of infection are relatively limited. A total of 605 patients with DLBCL were newly diagnosed at our institution between March 2009 and April 2017, and 132 of these patients developed pneumonia after treatment (21.8%). There was a significant difference in overall survival (OS) between the pneumonia and non-pneumonia groups (hazard ratio 4.819, 95% confidence interval: 3.109–7.470, p < 0.0001), with 5-year OS of 41% and 82%, respectively. Pulmonary involvement, Eastern Cooperative Oncology Group score > 1, and hypoalbuminemia were identified as independent risk factors for the development of pneumonia. We constructed a prediction model based on these three factors, and the area under the curve was 0.7083, indicating good discrimination. This model may help clinicians develop individualized strategies for preventing and treating post-chemotherapy pneumonia in patients with DLBCL.