Abstract
Hepatocellular carcinoma (HCC) is a cancer caused by inflammation, which affects the immune response and treatment outcomes. Finding new immune-related targets could improve HCC immunotherapy. New research suggests that TMEM family proteins can act as either tumor suppressors or oncogenes, but the role of TMEM101 in HCC development is unclear. This study conducted an analysis of TMEM101 mRNA expression and its correlation with clinical outcomes in HCC patients using RNA sequencing data from various open databases. Additionally, differences in TMEM101 expression in HCC cell lines and HCC tissue microarrays were examined using RT-qPCR, western blotting, and in situ hybridization staining. The findings presented herein offer initial evidence indicating a significant upregulation of TMEM101 mRNA expression in HCC, which is linked to a poorer prognosis. Furthermore, TMEM101 expression was found to be positively associated with the histological grade and clinical stage of HCC patients. Moreover, a notable reduction in promoter methylation of TMEM101 was observed in HCC patients. Cox regression analysis indicated that TMEM101 was an independent prognostic factor for overall survival (OS) in HCC patients. A nomogram incorporating TMEM101 and tumor stage was constructed and assessed. Comparative analysis with four established HCC diagnostic biomarkers (AFP, EFNA3, MDK, and SMYD5) using ROC curve and time-dependent ROC curves demonstrated the diagnostic potential of TMEM101 in HCC. Gene set enrichment analysis (GSEA) revealed a correlation between TMEM101 and the cell cycle, DNA replication, and repair signaling pathways, which were differentially enriched in the TMEM101 high expression phenotype. The findings from CIBERSORT analysis suggest that TMEM101's pro-tumor effect may be due to decreasing the number of anti-tumor immune cells (M1 macrophages and resting memory CD4+ T cells) and promoting M0 macrophage infiltration in the tumor microenvironment (TME). Overall, our study indicates that TMEM101 could serve as a promising diagnostic and prognostic biomarker for HCC.