Hypomethylation and the Resultant Overexpressed PARM1: a Biomarker for Poor Prognosis of Diffuse Large B-cell Lymphoma.

Abstract

Prostate androgen-regulated mucin-like protein (PARM1) is known to promote cell survival via protecting the cell surface, thus being involved in cancer development. The Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS database, LinkedOmics database, GeneMANIA database, and the Tumor Immune Estimation Resource (TIMER) database were accessed to explore the epigenetic regulation, prognostic value, biological functions and mechanisms of PARM1 in diffuse large B-cell lymphoma (DLBCL). Hypomethylation and resultant overexpression of PARM1 was found in DLBCL. The high-level expression of PARM1 was related to the poor outcome of DLBCL patients. PARM1 participated in DNA repair, cell cycle, and cellular response to stress. PARM1 was also associated with autophagy, apoptosis, Ras pathway, and MAPK cascade. Significant kinase targets of PARM1 included ATM, CDK1, and CDK2. Significant transcription factor targets of PARM1 involved ELK1, MYC and so on. Significant miRNA targets of PARM1 included miR21, miR202, miR323, and miR345. Further analysis suggested that the PARM1 regulated autophagy through the PI3K-Akt signaling. PARM1 was found to be correlated with immune cell infiltration, which indicated the important roles of PARM1 in microenvironment of DLBCL. Our study lays a foundation for further research on the impact of PARM1 in DLBCL tumorigenesis and precision therapy.