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The signaling of interleukin (IL)-23 and its receptor (IL-23R) play a crucial role in the development of cancers. However, the clinical significance of human serum soluble IL-23R (sIL-23R) and its relationship with IL-23 are still not explored in non-small cell lung cancer (NSCLC). In our study, sIL-23R was first identified in the serum of NSCLC patients, but not in healthy controls, by proteomics. The IL-23R mRNA and protein were upregulated in NSCLC cell lines and tissues tested by quantitative PCR, western blot analysis and immunohistochemistry. The levels of sIL-23R, IL-23, and IL-17 in 195 NSCLC patients' serum were determined by ELISA, and high levels of sIL-23R were significantly associated with advanced N stage (P = .039), clinical stage (P = .007), and poor 5-year survival rate. In vitro, sIL-23R was shown binding to IL-23 and the balance could affect patients' N and T stage, overall survival, and downstream cytokine IL-17 in a potential antagonistic relationship. Although sIL-23R, IL-23, and IL-17 were all associated with poor prognosis, only the sIL-23R/IL-23 ratio (hazard ratio, 1.945; 95% confidence interval, 1.147-3.299; P = .014) was found to be an independent factor for prognosis. Therefore, we identified fragments of soluble cytokine receptor of IL-23R with affinity ability to its natural ligand IL-23 in NSCLC patients' serum. The balance between the 2 antagonists can work as a potential prognostic serum marker., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Serous ovarian cancer is a major gynecologic malignancy with a poor 5‑year survival rate. However, little is known regarding the behavior and genetics of ovarian tumorigenesis. MicroRNAs (miRNAs) have been shown to be dysregulated in ovarian carcinomas. To assess the miRNA expression profiles in serous ovarian cancer, we defined the patterns of miRNA expression in 100 formalin‑fixed, paraffin‑embedded ovarian cancer tissues blocks as well as 50 corresponding normal oviduct tissues using miRNA microarray. MiRNA expression profiling showed that 63 miRNAs were downregulated and 43 miRNAs were upregulated in serous ovarian cancer tissues compared with control tissues. The expression of five dysregulated miRNAs was validated using quantitative polymerase chain reaction (RT‑qPCR). GO term and pathway analysis revealed that the biological process of the cell cycle was significantly enriched and the MAPK signaling pathway was highly involved in the progression of ovarian cancer. The results suggested that the aberrant expression of miRNAs is involved in ovarian carcinogenesis and thus these miRNAs may function as diagnostic and prognostic biomarkers.

BackgroundTo explore the evaluation value of systemic immune inflammation index (SII) in the prognosis of patients with alveolar hydatid disease, and establish a nomogram prediction model.MethodsCollect the clinical data of 351 patients undergoing hepatic alveolar hydatid surgery admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qinghai University from January 2015 to December 2020, calculate the SII value, and use the receiver operating characteristic curve (ROC curve) to determine According to the optimal clinical cut-off value of SII, patients were divided into two groups with high SII and low SII, and the relationship between SII and clinicopathological factors and prognosis of patients with alveolar echinococcosis was analyzed. Establish a nomogram prediction model based on independent risk factors for patient prognosis, and evaluate the prediction accuracy and discrimination ability of the nomogram through the consistency index (C-index) and calibration curve. The result is through the use of bootstrapping validation with 1,000 re-sampling Method for internal verification.ResultsThe ROC curve was used to determine the optimal cut-off value of SII before operation 761.192, and patients were divided into low SII group (n = 184) cases and high SII group (n = 167) cases. The 1, 3, and 5-year survival rates of patients with hepatic alveolar hydatid in the low SII group and the high SII group were 98.90%, 96.90%, 86.50% and 98.20%, 72.50%, 40.30%, respectively. The survival rate of worm disease patients was significantly better than that of the high SII group, and the overall survival rate difference between the two groups was statistically significant (P

Quantitative EEG (qEEG) delineates complex brain activities. Global field synchronization (GFS) is one multichannel EEG analysis that measures global functional connectivity through quantification of synchronization between signals. We hypothesized that preservation of global functional connectivity of brain activity might be a surrogate marker for good outcome in sudden cardiac arrest (SCA) survivors. In addition, we examined the relation of phase coherence and GFS in a mathematical approach. We retrospectively collected EEG data of SCA survivors in one academic medical center. We included 75 comatose patients who were resuscitated following in-hospital or out-of-hospital nontraumatic cardiac arrest between 2013 and 2017 in the intensive care unit (ICU) of National Taiwan University Hospital (NTUH). Twelve patients (16%) were defined as good outcome (GO) (CPC 1–2). The mean age in the GO group was low (51.6 ± 15.7 vs. 68.1 ± 12.9, p < 0.001). We analyzed standard EEG power, computed EEG GFS, and assessed the cerebral performance category (CPC) score 3 months after discharge. The alpha band showed the highest discrimination ability (area under curve [AUC] = 0.78) to predict GO using power. The alpha band of GFS showed the highest AUC value (0.8) to predict GO in GFS. Furthermore, by combining EEG power + GFS, the alpha band showed the best prediction value (AUC 0.86) in predicting GO. The sensitivity of EEG power + GFS was 73%, specificity was 93%, PPV was 0.67%, and NPV was 0.94%. In conclusion, by combining GFS and EEG power analysis, the neurological outcome of the nontraumatic cardiac arrest survivor can be well-predicted. Furthermore, we proved from a mathematical point of view that although both amplitude and phase contribute to obtaining GFS, the interference in phase variation drastically changes the possibility of generating a good GFS score.

Surgery combined with chemotherapy and precision medicine is the only potential treatment for patients with colorectal cancer liver metastases (CRLM). The use of modern molecular biotechnology to identify suitable biomarkers is of great significance for predicting prognosis and formulating individualized treatment plans for these patients. BRAF mutations, particularly V600E, are widely believed to be associated with poor prognosis in patients with metastatic CRC (mCRC). However, it is unclear which specific factors affect the prognosis of CRLM patients with BRAF mutations. It is also unknown whether patients with resectable CRLM and BRAF mutations should undergo surgical treatment since there is an increased recurrence rate after surgery in these patients. In this review, we combined the molecular mechanism and clinical characteristics of BRAF mutations to explore the prognostic significance and potential targeted therapy strategies for patients with BRAF-mutated CRLM.

Abstract Background Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently been identified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67 expression and prognosis in colorectal carcinoma. Methods Lgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectal carcinoma specimens. Selection of side population (SP) cells was performed by staining with Hoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected by immunofluorescence. Results Lgr5 expression was significantly higher in carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis (P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67 (r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low-staining cells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5 expression was strikingly stronger in Hoechst low-staining cells than in high-staining cells (P=0.001). Conclusions These findings suggest that Lgr5 may play an important role in the progression and prognosis of colorectal carcinoma, and may be a potential new therapeutic target for the treatment of colorectal cancer patients. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality.Methods and resultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P

Lung adenocarcinoma (LUAD) is a major subtype of non‐small‐cell lung cancer and accompanies high mortality rates. While the role of bilirubin metabolism in cancer is recognized, its specific impact on LUAD and patient response to immunotherapy needs to be elucidated. This study aimed to develop a prognostic signature of bilirubin metabolism‐associated genes (BMAGs) to predict outcomes and efficacy of immunotherapy in LUAD. We analysed gene expression data from The Cancer Genome Atlas (TCGA) to identify survival‐related BMAGs and construct a prognostic model in LUAD. The prognostic efficacy of our model was corroborated by employing TCGA‐LUAD and five Gene Expression Omnibus datasets, effectively stratifying patients into risk‐defined cohorts with marked disparities in survival. The BMAG signature was indeed an independent prognostic determinant, outperforming established clinical parameters. The low‐risk group exhibited a more favourable response to immunotherapy, highlighted by increased immune checkpoint expression and immune cell infiltration. Further, somatic mutation profiling differentiated the molecular landscapes of the risk categories. Our screening further identified potential drug candidates preferentially targeting the high‐risk group. Our analysis of critical BMAGs showed the tumour‐suppressive role of FBP1, highlighting its suppression in LUAD and its inhibitory effects on tumour proliferation, migration and invasion, in addition to its involvement in cell cycle and apoptosis regulation. These findings introduce a potent BMAG‐based prognostic indicator and offer valuable insights for prognostication and tailored immunotherapy in LUAD. [ABSTRACT FROM AUTHOR]

ObjectivesThis study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.BackgroundAF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.MethodsWe performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases).ResultsWe observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements.ConclusionsThe chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.

IRF family genes have been shown to be crucial in tumorigenesis and tumour immunity. However, information about the role of IRF in the systematic assessment of pan‐cancer and in predicting the efficacy of tumour therapy is still unknown. In this work, we performed a systematic analysis of IRF family genes in 33 tumour samples, including expression profiles, genomics and clinical characteristics. We then applied Single‐Sample Gene‐Set Enrichment Analysis (ssGSEA) to calculate IRF‐scores and analysed the impact of IRF‐scores on tumour progression, immune infiltration and treatment efficacy. Our results showed that genomic alterations, including SNPs, CNVs and DNA methylation, can lead to dysregulation of IRFs expression in tumours and participate in regulating multiple tumorigenesis. IRF‐score expression differed significantly between 12 normal and tumour samples and the impact on tumour prognosis and immune infiltration depended on tumour type. IRF expression was correlated to drug sensitivity and to the expression of immune checkpoints and immune cell infiltration, suggesting that dysregulation of IRF family expression may be a critical factor affecting tumour drug response. Our study comprehensively characterizes the genomic and clinical profile of IRFs in pan‐cancer and highlights their reliability and potential value as predictive markers of oncology drug efficacy. This may provide new ideas for future personalized oncology treatment. [ABSTRACT FROM AUTHOR]

Background & aimsHeritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis.MethodsWe conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent.ResultsBased on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7)).ConclusionsIn a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.

Background: The incidence of skin cutaneous melanoma (SKCM), one of the most aggressive and lethal skin tumors, is increasing worldwide. However, for advanced SKCM, we still lack an accurate and valid way to predict its prognosis, as well as novel theories to guide the planning of treatment options for SKCM patients. Lactylation (LAC), a novel post-translational modification of histones, has been shown to promote tumor growth and inhibit the antitumor response of the tumor microenvironment (TME) in a variety of ways. We hope that this study will provide new ideas for treatment options for SKCM patients, as well as research on the molecular mechanisms of SKCM pathogenesis and development. Methods: At the level of the RNA sequencing set (TCGA, GTEx), we used differential expression analysis, LASSO regression analysis, and multifactor Cox regression analysis to screen for prognosis-related genes and calculate the corresponding LAC scores. The content of TME cells in the tumor tissue was calculated using the CIBERSORT algorithm, and the TME score was calculated based on its results. Finally, the LAC–TME classifier was established and further analyzed based on the two scores, including the construction of a prognostic model, analysis of clinicopathological characteristics, and correlation analysis of tumor mutation burden (TMB) and immunotherapy. Based on single-cell RNA sequencing data, this study analyzed the cellular composition in SKCM tissues and explored the role of LAC scores in intercellular communication. To validate the functionality of the pivotal gene CLPB in the model, cellular experiments were ultimately executed. Results: We screened a total of six prognosis-related genes (NDUFA10, NDUFA13, CLPB, RRM2B, HPDL, NARS2) and 7 TME cells with good prognosis. According to Kaplan–Meier survival analysis, we found that the LAClow/TMEhigh group had the highest overall survival (OS) and the LAChigh/TMElow group had the lowest OS (p value < 0.05). In further analysis of immune infiltration, tumor microenvironment (TME), functional enrichment, tumor mutational load and immunotherapy, we found that immunotherapy was more appropriate in the LAClow/TMEhigh group. Moreover, the cellular assays exhibited substantial reductions in proliferation, migration, and invasive potentials of melanoma cells in both A375 and A2058 cell lines upon CLPB knockdown. Conclusions: The prognostic model using the combined LAC score and TME score was able to predict the prognosis of SKCM patients more consistently, and the LAC–TME classifier was able to significantly differentiate the prognosis of SKCM patients across multiple clinicopathological features. The LAC–TME classifier has an important role in the development of immunotherapy regimens for SKCM patients. [ABSTRACT FROM AUTHOR]

Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA–miRNA–mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration. [ABSTRACT FROM AUTHOR]

Background: Pharyngocutaneous fistula (PCF) is one of the most common complications of total laryngectomy. This study is to investigate the efficacy of a novel platform called transnasal negative pressure therapy (TNPT) in the management of PCF. Methods: We retrospectively reviewed 47 patients who underwent total laryngectomy between April 2015 and February 2021 and developed PCF in our hospital. We focused on the healing rate, dressing change frequency, and healing time between the TNPT and non‐TNPT groups. The 2 years overall survival (OS) was compared through the log‐rank test. Results: There were 18 patients in the TNPT group and 29 in the non‐TNPT group. There was no significant between‐group difference in the healing rate (chi‐square test). However, the frequency of dressing changes was significantly lower (p < 0.001) and the healing time was significantly shorter (p = 0.0194) in the TNPT group than in the non‐TNPT group. The 2‐year OS rate was significantly higher in the TNPT group (p = 0.0473, log‐rank test). Conclusion: TNPT promoted wound healing after surgery for PCF and improved the 2‐year OS rate. This tool is worthy of clinical application and promotion. [ABSTRACT FROM AUTHOR]

Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract cancer (BTC) is a highly aggressive malignancy with a poor prognosis; currently, limited biomarkers are available for early diagnosis and effective disease management. Therefore, it is essential to investigate reliable biomarkers for BTC patients. Peptidylarginine deiminase type 2 (PADI2) is a vital factor for post-translational modification (PTM) that catalyzes arginine to citrulline. It is crucial in several pathophysiological processes, such as autoimmune diseases and cancers. We evaluated the clinical significance of PADI2 expression in pathological stage I–III BTC patients. We observed that patients with high PADI2 protein expression are associated with poorer survival, including progress-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Our study highlighted, for the first time, a significant correlation between the PADI2 higher expression levels and unfavorable prognosis in BTC, which can be used to predict patients' survival outcomes. (1) Background: PADI2 is a post-translational modification (PTM) enzyme that catalyzes citrullination, which then triggers autoimmune disease and cancer. This study aimed to evaluate the prognostic value of peptidylarginine deiminase 2 (PADI2) protein expression in biliary tract cancer (BTC) patients. (2) Methods: Using immunohistochemistry, the PADI2 protein expression in BTC tissues was analyzed. The correlations between PADI2 protein expression and clinicopathologic characteristics were analyzed using Chi-square tests. The Kaplan–Meier procedure was used for comparing survival distributions. We used Cox proportional hazards regression for univariate and multivariate analyses. From 2014 to 2020, 30 resected BTC patients were enrolled in this study. (3) Results: Patients with high PADI2 protein expression were associated with shorter progress-free survival (PFS; p = 0.041), disease-specific survival (DSS; p = 0.025), and overall survival (OS; p = 0.017) than patients with low PADI2 protein expression. (4) Conclusions: The results indicated that PADI2 protein expression was an independent poor prognostic factor for BTC patients regarding PFS, DSS, and OS. [ABSTRACT FROM AUTHOR]