TMC5 as a Marker of Tumor-Associated Telocytes in Hepatocellular Carcinoma.

Abstract

Background: Tumor-associated telocytes (TATCs) perform a pivotal role in hepatocellular carcinoma (HCC) progression and correlate with poor patient outcomes. This study aims to identify specific markers of TATCs in HCC using single-nucleus RNA sequencing (snRNA-seq) and transcriptomic analyses.

Methods: Comprehensive snRNA-seq and transcriptomic profiling were performed on HCC and adjacent non-cancerous tissues to detect differential expressed genes (DEGs) in TATCs. Bioinformatics tools, including STING and Cytoscape software, were employed to analyze protein-protein interactions and hub genes. Immune cell interactions were assessed via ligand-receptor network analysis.

Result: TATCs constituted 0.35% of cells in HCC tissues, with reduced proportions compared to para-cancerous tissues (0.35% vs 8.19%). Hub genes, including TOP2A (DNA topoisomerase Ⅱ alpha), BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B), KIF11 (kinesin family member 11), and CENPF (centromere protein F) were identified in telocytes (TCs). Transcriptomics revealed 622 upregulated and 758 downregulated genes in TATCs versus TCs. TMC5 (transmembrane channel like 5) and SLC35F3 (solute carrier family 35 member F3) emerged as unique TATCs biomarkers, revealing significant associations with poor overall survival (OS) in HCC patients (HR = 1.499 for TMC5; HR = 1.562 for SLC35F3).

Conclusion: TMC5 and SLC35F3 are promising biomarkers for TATCs in HCC, warranting further validation to explore their clinical and therapeutic implications.