Analyses of KDM4 Family for Prognostic Values and Immune Infiltration in Patients with Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the leading lethal cancers. Varieties of treatment methods have been developed without promising results to reduce mortality in patients with advanced HCC. KDM4 genes ( KDM4s ) are associated with multiple malignancies. Aim: This study aimed to investigate the role of KDM4s in the prognostic prediction and treatment of HCC. Methods: Multi-omics analyses were used to explore differential expression, prognostic value, genetic alteration, associated signaling pathways, microRNA (miRNA) targets, and immune cell infiltration of KDM4s in patients with HCC. Results: KDM4s messenger ribonucleic acid (mRNA) levels in various common cancer cell lines were obtained. KDM4A-C in liver cancer cell lines ranked 20, 15, and 29, respectively, within 34 cancer cell lines. KDM4 upregulation was demonstrated in HCC compared to adjacent normal tissue by The U niversity of AL abama at Birmingham CAN cer data analysis Portal (UALCAN) and confirmed by the hepatocellular cell carcinoma database (HCCDB). High KDM4A and KDM4C expression indicated poor overall survival (OS), whereas high KDM4B expression was significantly associated with good OS. High KDM4C expression indicated poor recurrence-free survival. Genetic alteration and biological interaction network of KDM4s showed that KDM4s play vital roles in metabolic pathways, molecular signaling, and many diseases. The miRNA targets and immune cell infiltration associated with KDM4s were explored and may provide value as therapeutic targets in HCC. Conclusion: KDM4s are promising prognostic biomarkers for survival and could be potential molecules for targeted therapy or immunotherapy in patients with HCC.