MUTYH is a potential prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma

Abstract

Background

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The development of biomarkers for early detection and monitoring of HCC has not shown significant progress. Meanwhile, the second adenomatous polyposis-related gene, MUTYH, which encodes a DNA glycosylase, has been observed in its contribution to oxidative DNA damage repair. Abnormal expression of MUTYH can reduce cell survival rate. Therefore, this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.

Materials and methods

Using The Cancer Genome Atlas (TCGA) data, we analyzed the prognostic value of MUTYH in HCC. We used logistic regression, Wilcoxon signed-rank test, and Kruskal–Wallis test to examine MUTYH expression concerning clinical-pathologic characteristics. Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC. The enrichment analysis (GSEA) was used to determine the critical pathways associated with MUTYH. The single-sample gene set enrichment analysis (ssGSEA) was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.

Results

The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that all differentially expressed genes (DEGs) between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction, cell cycle, oocyte meiosis, gap junction, and DNA replication. Group analysis revealed the signals of their open access. The neuron system, M phase, DNA repair, Rho GTPase effector, and cell cycle checkpoints were significantly enriched. ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells, NK cells, and T helper cells. Moreover, a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells (DCs) and cytotoxic cells.

Conclusions

MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues. The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.