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Background: In the era of immunotherapy, predictive or prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC) are urgently needed. Metabolic reprogramming in the tumor microenvironment (TME) is a non-negligible reason for the low therapeutic response to immune checkpoint inhibitor (ICI) therapy. We aimed to construct a metabolism-related gene prognostic index (MRGPI) for HNSCC bridging metabolic characteristics and antitumor immune cycling and identified the immunophenotype, genetic alternations, potential targeted inhibitors, and the benefit of immunotherapy in MRGPI-defined subgroups of HNSCC. Methods: Based on The Cancer Genome Atlas (TCGA) HNSCC dataset (n = 502), metabolism-related hub genes were identified by the weighted gene co-expression network analysis (WGCNA). Seven genes were identified to construct the MRGPI by using the Cox regression method and validated with an HNSCC dataset (n = 270) from the Gene Expression Omnibus (GEO) database. Afterward, the prognostic value, metabolic activities, genetic alternations, gene set enrichment analysis (GSEA), immunophenotype, Connectivity map (cMAP), and benefit of immunotherapy in MRGPI-defined subgroups were analyzed. Results: The MRGPI was constructed based on HPRT1 , AGPAT4 , AMY2B , ACADL , CKM , PLA2G2D , and ADA. Patients in the low-MRGPI group had better overall survival than those in the high-MRGPI group, consistent with the results in the GEO cohort (cutoff value = 1.01). Patients with a low MRGPI score display lower metabolic activities and an active antitumor immunity status and more benefit from immunotherapy. In contrast, a higher MRGPI score was correlated with higher metabolic activities, more TP53 mutation rate, lower antitumor immunity ability, an immunosuppressive TME, and less benefit from immunotherapy. Conclusion: The MRGPI is a promising indicator to distinguish the prognosis, the metabolic, molecular, and immune phenotype, and the benefit from immunotherapy in HNSCC. [ABSTRACT FROM AUTHOR]

The overall survival of patients with lower grade glioma (LGG) that might develop into high-grade malignant glioma shows marked heterogeneity. The currently used clinical evaluation index is not sufficient to predict precise prognostic outcomes accurately. To optimize survival risk stratification and the personalized management of patients with LGG, there is an urgent need to develop an accurate risk prediction model. The TCGA-LGG dataset, downloaded from The Cancer Genome Atlas (TCGA) portal, was used as a training cohort, and the Chinese Glioma Genome Atlas (CGGA) dataset and Rembrandt dataset were used as validation cohorts. The levels of various cancer hallmarks were quantified, which identified glycolysis as the primary overall survival-related risk factor in LGGs. Furthermore, using various bioinformatic and statistical methods, we developed a strong glycolysis-related gene signature to predict prognosis. Gene set enrichment analysis showed that in our model, high-risk glioma correlated with the chemoradiotherapy resistance and poor survival. Moreover, based on established risk model and other clinical features, a decision tree and a nomogram were built, which could serve as useful tools in the diagnosis and treatment of LGGs. This study indicates that the glycolysis-related gene signature could distinguish high-risk and low‐risk patients precisely, and thus can be used as an independent clinical feature. [ABSTRACT FROM AUTHOR]

Background: The discovery of reliable cancer biomarkers could tune a diagnosis and improve the way patients are treated. However, many cancers lack robust biomarkers. C1QTNF6 has been preliminarily elucidated for its role in some tumors. However, no pan-cancer analysis has been performed to comprehensively explore the value of C1QTNF6. Methods: Data from the TCGA database, GTEx database stored in the USUC Xena were used for analyzing the profiles of C1QTNF6 expression in normal and tumor tissues in pan-cancer. Subsequently, the gene alteration rates of C1QTNF6 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between C1QTNF6 mRNA expression and copy number alterations (CNA) and methylation was determined. Survival analyses of C1QTNF6 were carried out. Moreover, the tumor biological and immunological characteristics of C1QTNF6 were clarified in the forms of the correlation between C1QTNF6 expression and hallmark Pathway scores in MsigDB database, immune cell infiltration, immune-related genes. We conducted a GSEA of C1QTNF6 to illustrate its potential biological functions. In addition, GDSC2 data with 198 drugs were adopted to explore drug sensitivity with the change of C1QTNF6 expression. Result: C1QTNF6 was overexpressed in many types of cancer, Survival analysis showed that C1QTNF6 independently served as a prognostic indicator for poor survival in many tumors. Besides, we also identified a positive correlation between C1QTNF6 and cancer hallmark pathway score, tumor microenvironment related pathways score (TMEp score), and immune characteristic. In terms of drug sensitivity analysis, we found higher expression level of C1QTNF6 predicts a high IC50 value for most of 198 drugs which predicts drug resistance. Conclusions: Our study provides a new biological marker for pan-cancer, which is beneficial to the diagnosis and treatment of cancer, which bring a new therapeutic target for tumors. [ABSTRACT FROM AUTHOR]

Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. However, the methylation status, expression, and prognostic role of ZNF671 in solid tumors remain unclear. The aim of this study was to explore the relationship between ZNF671 and the prognosis of patients with solid tumors. We performed a pan-cancer analysis of the methylation status and mRNA and protein expression of ZNF671 using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. We further evaluated the prognostic value of ZNF671 expression among numerous cancer types using the "Kaplan–Meier plotter" (KM plotter) database. We found that downregulation of ZNF671 is associated with hypermethylation of its promoter. Survival analysis established that the downregulation of ZNF671 predicts poor prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) solid tumors. CCK-8 and Transwell functional assays showed that ZNF671 could inhibit tumor cell proliferation, migration, and invasion. These results indicate that ZNF671 is an excellent predictive factor for BRCA, CESC, HNSC, KIRP, LUAD, PAAD, SARC, and UCEC solid tumors and may play crucial roles in the development and progression of these tumors. [ABSTRACT FROM AUTHOR]

Our data demonstrate for the first time that the tight junction protein JAM-A induces EMT of NPC in vitro and in vivo via the PI3K/Akt pathway.Junctional adhesion molecule-A (JAM-A) is preferentially concentrated at tight junctions and influences epithelial cell morphology and migration. Epithelial-to-mesenchymal transition (EMT) is the conversion process of epithelial cells into mesenchymal cells, and it plays an important role in the invasiveness and metastasis of various cancers. However, the role of JAM-A in regulating the invasive behaviours of human nasopharyngeal carcinoma (NPC) is unknown. In this study, we found that JAM-A upregulation induced EMT, whereas silencing of endogenous JAM-A expression reversed EMT. Furthermore, upregulation of JAM-A led to EMT via activation phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. PI3K inhibitors blocked JAM-A-induced EMT, suggesting that the kinase acts downstream of JAM-A. Finally, results from 172 human patients with NPC showed that high expression levels of JAM-A correlated with metastasis and poor prognosis in NPC. Taken together, these results suggest that high JAM-A expression positively correlates with poor prognosis in patients with NPC, and induces EMT of NPC cells in vitro and in vivo via the PI3K/Akt pathway. These data indicate novel functions in the JAM-A repertoire, and have clinical implications for the treatment of patients with NPC. [ABSTRACT FROM AUTHOR]