TTC36 as a prognostic biomarker in nonmetastatic hepatocellular carcinoma: A TCGA-based cohort study

Nonmetastatic hepatocellular carcinoma (nMHC) is a common form of primary liver cancer with distinct molecular and clinical characteristics. Tetratricopeptide repeat domain 36 (TTC36), a gene associated with various cancer types, has been implicated in tumorigenesis, but its role in nMHC is not fully understood. This study investigates the role of TTC36 in nMHC using The Cancer Genome Atlas data. Gene expression data and clinical information for nMHC patients were retrieved from the The Cancer Genome Atlas database. Differential expression of TTC36 in tumor and normal tissues was assessed, and diagnostic accuracy was evaluated using receiver operating characteristic analysis. Kaplan-Meier and Cox regression analyses determined the prognostic value of TTC36. Differentially expressed genes related to TTC36 were identified and analyzed for functional enrichment via Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis. A protein-protein interaction network was constructed, and immune infiltration correlations were examined using the tumor immune estimation resource database. TTC36 expression was significantly lower in nMHC tissues compared to normal liver tissues and adjacent nontumor tissues, with an area under the curve of 0.960 (95% CI: 0.941-0.978) for diagnosis. High TTC36 expression correlated with older age, obesity, early T stages, early histological grade, early clinical stages but was inversely related to alpha-fetoprotein. High TTC36 expression independently predicted better overall survival (HR = 0.536, 95% CI: 0.365-0.787, P = .001) and was associated with improved disease-specific survival, disease-free interval, and progression-free interval (P < .05). Gene set enrichment analysis indicated that high TTC36 expression suppressed peroxisome, metabolism, glycolysis/gluconeogenesis, steroid hormone biosynthesis, and primary bile acid biosynthesis. Negative correlations were observed between TTC36 expression and immune cell infiltration. TTC36 is a promising prognostic biomarker in nonmetastatic hepatocellular carcinoma. Its expression correlates with improved patient outcomes and reduced immune cell infiltration, suggesting its potential as a therapeutic target for modulating the tumor immune microenvironment.