Background: Mediator complex subunit 8 (MED8) is known for its role in encoding a subunit of the mediator complex (MED), that is critical for transcription. MED8 is significantly expressed in various tumors and has been correlated with an unfavorable prognosis. Nevertheless, no relationships have been found between MED8 and the clinical characteristics of hepatocellular carcinoma (HCC).
Methods: To conduct an evaluation of correlations between clinicopathologic characteristics and MED8 expression, the logistic regression, Wilcoxon signed-rank test, and Kruskal-Wallis test were used. To perform analysis of factors contributing to prognosis, the Kaplan-Meier approach and the Cox regression analyses were used. A nomogram on the basis of a Cox multivariate analysis was employed to anticipate the influence of MED8 on patient prognosis. The receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to assess the prognostic value of MED8. Both immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were applied to reveal significant enrichment differences among TCGA data. Quantitative RT-PCR (qRT-PCR) and western blotting were used to verify the difference in the expression of MED8 in normal and hepatocellular carcinoma cells. The immunohistochemical method was used to validate the MED8 expression in tumor and adjoining tissues of HCC patients.
Results: A univariate analysis showed that high MED8 expression predicts poor disease-specific survival (DSS) (HR: 2.57; 95% confidence interval (CI) 1.62, 4.07; P<0.001). Multivariate regression analysis showed that high MED8 (adjusted HR: 3.032 (1.817, 5.060); P<0.001) expression and M stage (adjusted HR=4.075 (1.179-14.091) for M1 vs. M0, P=0.026) served as prognostic indicators of unfavorable overall survival in an independent manner in patients with HCC. The C-index for the nomogram was 0.732 (95% CI: 0.698, 0.766) and the AUC of MED8 was 0.817 (95% CI: 0.778, 0.857). Functional analysis showed that the cell cycle checkpoints, p53 dependent G1-DNA damage response, mitotic G1-G1-S phases, and mitotic G2-G2-M phases, were significantly enriched in DEGs associated with MED8 expression. Th2 cells were positively correlated with MED8 expression.
Conclusions: MED8 predicts poor prognosis in HCC, possibly through modulating the cell cycle and Th2 cells.
Keywords: Mediator complex subunit 8; diagnostic biomarker; hepatocellular carcinoma; mediator; prognosis.
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