The Prognostic Value of AT-Rich Interaction Domain (ARID) Family Members in Patients with Hepatocellular Carcinoma.

Objective: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies with a poor prognosis. The AT-rich interaction domain (ARID) family plays an essential regulatory role in the pathogenesis and progression of cancers. This study aims to evaluate the prognostic value and clinical significance of human ARID family genes in HCC.

Methods: ONCOMINE and The Cancer Genome Atlas (TCGA) databases were employed to retrieve ARIDs expression profile and clinicopathological information of HCC. Kaplan-Meier plotter and MethSurv were applied to the survival analysis of patients with HCC. CBioPortal was used to analyze genetic mutations of ARIDs. Gene Expression Profiling Interactive Analysis (GEPIA) and Metascape were used to perform hub gene identification and functional enrichment.

Results: Expression levels of 11 ARIDs were upregulated in HCC, and 2 ARIDs were downregulated. Also, 4 ARIDs and 5 ARIDs were correlated with pathologic stages and histologic grades, respectively. Furthermore, higher expression of ARID1A, ARID1B, ARID2, ARID3A, ARID3B, ARID5B, KDM5A, KDM5B, KDM5C, and JARID2 was remarkably correlated with worse overall survival of patients with HCC, and the high ARID3C/KDM5D expression was related to longer overall survival. Multivariate Cox analysis indicated that ARID3A, KDM5C, and KDM5D were independent risk factors for HCC prognosis. Moreover, ARIDs mutations and 127 CpGs methylation in all ARIDs were observed to be significantly associated with the prognosis of HCC patients. Besides, our data showed that ARIDs could regulate tumor-related pathways and distinct immune cells in the HCC microenvironment.

Conclusions: ARIDs present the potential prognostic value for HCC. Our findings suggest that ARID3A, KDM5C, and KDM5D may be the prognostic biomarkers for patients with HCC.