Comprehensive pan-cancer analysis reveals VSIR as a candidate immunologic, diagnostic, and prognostic biomarker.

OBJECTIVES: Being a checkpoint, the expression level of V-set immunoregulatory receptor (VSIR) serves as an indicator of the extent of immunosuppression. Our objective was to undertake a pan-cancer analysis to examine the expression, genetic alterations, prognosis, and immunologic features associated with VSIR. METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), GEPIA2, UALCAN, OncoDB, Human Protein Atlas (HPA), STRING, DAVID, cell culture, clinical sample collection, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used. RESULTS: This study comprehensively assessed VSIR across 33 cancers using TCGA and GTEx databases. Differential expression analysis revealed elevated VSIR in several cancers, notably in cholangiocarcinoma, esophageal carcinoma, kidney renal cell carcinoma, and liver hepatocellular carcinoma, while decreased expression was observed in various others. Prognostic analysis highlighted its significant association with reduced overall survival (OS) in ESCA and LIHC. Investigation into cancer stages demonstrated a correlation between VSIR expression and stage in ESCA and LIHC. Promoter methylation analysis indicated decreased VSIR methylation levels in tumors, implicating a role in oncogenesis. Furthermore, subcellular localization predictions, Tumor Mutational Burden (TMB), and Microsatellite Instability (MSI) correlations revealed intriguing insight into VSIR's function. Notably, a positive correlation was identified between VSIR expression and various immune cells in both cancers. Protein-protein interaction (PPI) network construction and gene enrichment analysis elucidated VSIR-associated dysregulated pathways, emphasizing its possible involvement in diverse pathways. Finally, experimental validation using LIHC clinical samples and cell lines confirmed elevated VSIR expression, supporting its oncogenic role. CONCLUSION: Collectively, these findings present a comprehensive understanding of VSIR's diverse roles and potential clinical implications in ESCA and LIHC.

Screening of four signature genes for clinical testing through bioinformatics and in vitro methods in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is the 6th most common cancer around the globe; its underlying molecular mechanisms and accurate molecular markers are still lacking. In this study, we explored hub genes and their potential signaling pathways through which these genes participate in the development of HNSC. The GSE23036 gene microarray dataset was attained from the GEO (Gene Expression Omnibus) database. Hub genes were identified via the Cytohubba plug-in application of the Cytoscape. The Cancer Genome Atlas (TCGA) datasets and cell lines (HOK and FuDu) were used to evaluate expression variations in the hub genes. Moreover, promoter methylation, genetic alteration, gene enrichment, miRNA network, and immunocyte infiltration analysis were also performed to confirm the oncogenic role and biomarker potential of the hub genes in HNSC patients. Based on the hub gene analysis results, four hub genes, including KNTC1 (Kinetochore Associated 1), CEP55 (Centrosomal protein of 55 kDa), AURKA (Aurora A Kinase), and ECT2 (Epithelial Cell Transforming 2), with the highest degree scores were denoted as hub genes. All these four genes were significantly up-regulated in HNSC clinical samples and cell lines relative to their counterparts. Overexpression of KNTC1, CEP55, AURKA, and ECT2 was also associated with poor survival and various clinical parameters of the HNSC patients. Methylation analysis through targeted bisulfite sequencing of HOK and FuDu cell lines revealed that the overexpression of KNTC1, CEP55, AURKA, and ECT2 hub genes was due to their promoter hypomethylation. Moreover, higher expressions of KNTC1, CEP55, AURKA, and ECT2 were positively correlated with the abundance of the CD4+ T cells and macrophage while with the reduction of CD8+ T cells in HNSC samples. Finally, gene enrichment analysis showed that all hub genes are involved in "nucleoplasm, centrosome, mitotic spindle, and cytosol" pathways. In conclusion, the KNTC1, CEP55, AURKA, and ECT2 genes could be potential biomarkers for HNSC patients and provide a novel insight into the diagnosis and treatment of the disease.

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.