Comprehensive analyses of prognostic biomarkers and immune infiltrates among histone lysine demethylases (KDMs) in hepatocellular carcinoma

Background: Histone lysine demethylases (KDMs) are closely related to the occurrence and development of different tumors through epigenetic mechanisms. However, the prognosis and immune infiltration of KDMs in hepatocellular carcinoma (HCC) remain undefined.

Methods: In the current study, we analyzed the expression of KDMs on HCC patients using the Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, Metascape, GSEA, and TIMER databases. Finally, we investigated KDM expression in HCC by qRT-PCR, Western blotting, and IHC.

Results: We found that KDM3A/3B/5A/5B and KDM6A were upregulated in HCC patients, while KDM6B and KDM8 were downregulated. The high expressions of KDM1A/2B/3B/5B/5C were markedly related to tumor stages and grades of HCC patients. The abnormal expression of KDM1A/1B/3A/4A/5A/5C/6A/6B/7A and KDM8 were associated with HCC patients' prognosis. Also, we found that HCC tissues presented higher expression levels of KDM1A/2A/5A/5B and lower expression levels of KDM6B. The function of KDMs was primarily related to the histone demethylase activity and cell cycle, p53 signaling pathway, pathways in cancer, transcriptional mis-regulation in cancer, viral carcinogenesis, and FoxO signaling pathway. Furthermore, we indicated that the pathways most involved were the mitotic spindle and DNA repair. Additionally, we found that the expression of KDM1A/1B/3A/4A/5B/5C and KDM6A were significantly correlated with HCC immune infiltration.

Conclusions: Overall, our current results indicated that KDM1A/1B/3A/4A/5B/5C and KDM6A could be novel prognostic biomarkers and provide insights into potential immunotherapy targets to HCC patients.