Decaprenyl Diphosphate Synthase Subunit 1 (PDSS1): A Potential Prognostic Biomarker and Immunotherapy-Target for Hepatocellular Carcinoma.

Purpose: PDSS1 (decaprenyl diphosphate synthase subunit 1) plays an important role in the progression of several types of tumor. However, the biological functions of PDSS1 remain unclear in patients with hepatocellular carcinoma (HCC). In this study, We attempted to determine the role of PDSS1 in predicting the survival and efficacy of immunotherapy for HCC patients.

Methods: We analyzed the expression of PDSS1 in pan-cancer by Tumor Immune Estimation Resource (TIMER) and UALCAN database. Next, we investigated the correlations between the expression and potential prognostic value of PDSS1 in pan-cancer by Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier plotter and further confirmed our finding in our study of 139 patients with HCC. Furthermore, we correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules in HCC tissue by TIMER. Finally, its potential immune-related mechanism was explored by Gene Set Enrichment Analysis (GSEA).

Results: Multiple datasets demonstrate that PDSS1 is up-regulated in HCC tissues compared with adjacent tissues, which was validated at mRNA (databases) and protein levels (our cohort). Patients with higher PDSS1 expression had shorter overall survival and relapse-free survival. In addition, PDSS1 expression was positively related to early recurrence and served as an independent poor prognostic factor for HCC. Patients with higher PDSS1 expression had lower CD8+ T cells in HCC tissue, and PDSS1 deteriorates T cell exhaustion by promoting T cell surface inhibitory receptors' secretion and immunosuppressive cell proliferation. Furthermore, PDSS1 was positively correlated with the WNT, TGFβ, VEGF, and other signaling pathways in HCC.

Conclusion: PDSS1 is a potential prognostic biomarker and immunotherapy target for hepatocellular carcinoma.