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A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer.

ABSTRACT: Hepatitis A virus cellular receptor (HAVCR1) is a type-1 integral membrane glycoprotein that plays a key role in immunity and renal regeneration and is abnormally expressed in various tumor types. Nonetheless, the function of HAVCR1 in pan-cancer remains unknown. In this study, we comprehensively analyzed the expression and promoter methylation level of HAVCR1 and assessed the immune cell infiltration, correlation between stromal and immune cell admixture, CD (Cluster of Differentiation) and HAVCR1 expression and prognostic value of HAVCR1 mRNA expression in Liver hepatocellular carcinoma (LIHC) and Pancreatic adenocarcinoma (PAAD). Our results showed that HAVCR1 was overexpressed while the promoter methylation of HAVCR1 was decreased in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 was associated with increased infiltration of B cells, CD8 cells, macrophages, neutrophils and Dendritic cells in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 expression was positively correlated with the immune, stromal and estimate scores of Pancreatic adenocarcinoma and the stromal and estimate scores of Liver hepatocellular carcinoma. Furthermore, HAVCR1 expression was correlated with other immune molecules such as HHLA2 (Human endogenous retrovirus-H long terminal repeat-associating protein 2), CD44 and TNFRSF4 (TNF Receptor Superfamily Member 4) in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. During Kaplan-Meier analysis, high HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma correlated with poor survival. A marginally significant p-value (p = 0.051) was obtained when the relationship between HAVCR1 expression in Liver hepatocellular carcinoma and prognosis was analyzed, attributed to the small sample size. Overall, we provided compelling evidence that HAVCR1 could be a prognostic and diagnostic marker for Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.

SUBMITTER: Liu S

PROVIDER: S-EPMC9213751 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundZinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated.MethodsIn this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients.ResultsThe pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects.ConclusionsZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.

Project description:Chromosome 16 open reading frame 54 (C16orf54) is a protein coding gene, showing a biased expression in the bone marrow, lymph node, and 11 other tissues. Reports on the function of C16orf54 in the onset and development of tumours remain scarce. Clinical information and tumour expression profile data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) were utilized to determine the relationship between C16orf54 expression and prognosis, diagnosis, immune microenvironment, heterogeneity, and stemness across pan-cancer. The findings ascertained that C16orf54 was expressed at a low level in most cancers. Furthermore, C16orf54 could distinguish between cancer and normal tissues with high accuracy in most cancers, and the prognostic significance of low C16orf54 mRNA levels differs across cancers. C16orf54 expression was positively linked to the stromal, immune, and ESTIMATE scores. On the other hand, C16orf54 was reported to be negatively correlated with tumour purity in most cancers. Further, C16orf54 expression was positively correlated with immune cell infiltration and the expression of immune regulatory genes, including chemokines, receptors, major histocompatibility complexes, immune inhibitory, and immune stimulatory genes, in most cancers. Additionally, C16orf54 expression was significantly associated with tumour heterogeneity indicators, such as tumour mutation burden (TMB) and microsatellite instability (MSI), and was significantly correlated with DNAss and RNAss tumour stemness indicators. Moreover, Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis, as well as Gene Set Enrichment analysis (GSEA), revealed that C16orf54 expression was closely linked to the signalling pathways of immune cells and factors. The integrated analysis of C16orf54 indicates it as a potential prognostic, diagnostic, and immune marker, which could be adopted as a novel target for adjuvant immunotherapy across pan-cancer.

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A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer.

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