Identification of CCDC58 as a potential predictive biomarker of immune cell infiltration in hepatocellular carcinoma.

Abstract

Background: Mitochondrial dynamics play a critical role in the proper functioning of both the innate and adaptive immune systems. Coiled-coil domain-containing 58 (CCDC58), a mitochondrial-related gene, has been implicated in various diseases, including cancer and infections. However, its predictive value in immune cell infiltration in hepatocellular carcinoma (HCC) remains unexplored.

Methods: In this study, RNA-seq data from The Cancer Genome Atlas and multiple online datasets were analyzed to explore the correlation between CCDC58 and clinicopathological features, prognosis, related signaling pathways and immune cell infiltration in HCC. Furthermore, primary T cells were isolated and cell experiments such as cytotoxic assays and transwell assays were conducted to verify pivotal conclusions.

Results: We found that CCDC58 expression levels were significantly increased in HCC tissues. High CCDC58 expression in HCC tissues was significantly correlated with the patients' TNM stage, histologic grade, AFP level, tumor status, and poor clinical outcomes. Furthermore, the high expression of CCDC58 conferred a decreased immune activated phenotype and poor immune cell infiltration, and was strongly associated with expression of immune cell exhaustion markers in HCC. After the knockdown of CCDC58 in HCC cell lines, we observed that cytotoxicity of primary T cells increased via decreasing PD-1 expression on T cells and migration ability of primary T cell enhanced.

Conclusion: Our study indicated that CCDC58 might serve as a potential predictive biomarker of immune cell infiltration in HCC and is correlated with poor prognosis in HCC patients.