Systematic analysis of the expression profile and prognostic significance of m6A regulators and PD-L1 in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. N6-methyladenosine (m6A) modification has dual biological functions in RNA modification and plays an important role in HCC.

Methods: The GEO, TCGA, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal for Cancer Genomics, STRING and TIMER2 databases were used for bioinformatic analyses. Quantitative polymerase chain reaction and western blotting were used to detect the expression of m6A regulators in HCC tissues.

Results: The transcription of m6A regulators was upregulated in patients with HCC, and overexpression of YTHDF1/2, YTHDC1, RBM15 and METTL3 was significantly correlated with clinical stages of HCC. In addition, downregulation of ZC3H13 and METTL14 and upregulation of other m6A regulators were associated with a poor prognosis. A high mutation rate (89%) of m6A regulators was also observed in patients with HCC, and mutations in methylation regulators were associated with poor overall survival and disease-free survival. Finally, the expression of the YTHDF family was significantly associated with immune infiltration in the HCC microenvironment.

Conclusion: m6A regulators and programmed death-ligand 1 may play an important role in the tumorigenesis and immune invasion and escape of HCC and may be risk factors affecting the survival of patients with HCC.