The collagen-modifying enzyme GLT25D1 is a prognostic indicator related to immunosuppression and malignant phenotypes in hepatocellular carcinoma.

BACKGROUND

The collagen β (1-O) glycosyltransferase 25 domain 1 (GLT25D1), a crucial collagen-modifying enzyme (CME), plays a pivotal role in multiple pathophysiological processes. However, its prognostic and biological roles in hepatocellular carcinoma (HCC) have not been reported.

METHODS

CME-related genes (CMEGs) were obtained from the Molecular Signatures Database (MSigDB), differentially expressed CMEGs (DECMEGs) and prognostic ones were identified. GLT25D1 expression was determined at the mRNA and protein levels in multiple datasets and in our HCC cohort. Its prognostic performance was evaluated and the immune microenvironment was investigated. The effects of GLT25D1 on tumorigenesis were further explored via in vitro and in vivo experiments.

RESULTS

Four potential prognosis-associated DECMEGs, including GLT25D1, were identified. GLT25D1 was noticeably up-regulated in HCC tissues and significantly associated with advanced tumor grade and stage. Enrichment analysis revealed that GLT25D1 could participate in regulating immune responses and various carcinogenic processes. HCC patients with high GLT25D1 expression had decreased CD8 T cells and increased M0 macrophages, leading to an immunosuppressive microenvironment. Our in vivo and in vitro experiments confirmed the increased GLT25D1 expression, and GLT25D1 knockdown impaired the HCC malignant phenotypes.

CONCLUSIONS

Our results showed that GLT25D1 could be a carcinogenic indicator reflecting poor prognosis and might serve as a potential risk biomarker for HCC patients.