The Clinicopathological Value and Immunological Role of miR-21/PCYOX1 Axis in Hepatocellular Carcinoma

The Clinicopathological Value and Immunological Role of miR-21/PCYOX1 Axis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a major global health challenge due to its increasing incidence and mortality rates.. Overexpression of microRNA-21 (miR-21) is associated with a poor prognosis in liver cancer patients but the mechanism by which it affects cancer metabolism is unknown. This study uses multi-omics analysis and cross-database validation to determine the effect of miR-21/ PCYOX1 (prenylcysteine oxidase 1) axis on the clinicopathology and tumor immunology in HCC. The diagnostic and prognostic significance of biomarkers is determined based on The Cancer Genome Atlas (TCGA) repository.
Co-expressed genes of miR-21 and Gene Set Enrichment Analysis (GSEA) are analyzed using LinkedOmics. Validation datasets are collected from TCEA (The Cancer RNA Editome Atlas), the Gene Expression Omnibus (GEO) and the Human Protein Atlas (HPA). Pharmacogenetics analysis for miRNAs and coding genes respectively use the GEO and Genomics of Drug Sensitivity in Cancer (GDSC) database.
Higher miR-21 expressions are noted in a HCC tumor than in normal tissue. Male HCC patients exhibit higher levels of miR-21 than female patients. Male HCC patients with high miR-21 levels have a shorter overall survival time. miR-21 exhibits complementary base pairing with the 3’un-translational region (3’UTR) of several key metabolic genes but only PCYOX1 is correlated negatively with miR-21. Low expressions of PCYOX1 in HCC than normal are observed and are associated with a shorter overall survival time. Validation dataset verified the diagnostic and prognostic significance of miR-21/PCYOX1. High miR-21 and low PCYOX1 levels are associated with an immunosuppressive microenvironment. Pharmacogenetics analysis identifies drugs candidates for cells with low PCYOX1 and high miR-21 expressions. This study shows that miR-21/ PCYOX1 axis is a biomarker panel for the diagnosis, prognosis and an immunosuppressive microenvironment.