Comprehensive analysis of the tumor-promoting effect and immune infiltration correlation MAZ from pan-cancer to hepatocellular carcinoma.

Abstract

Myc-associated zinc-finger protein (MAZ) is a transcription factor, which has been confirmed to be abnormally expressed in many tumors and involved in regulating the proliferation, migration, apoptosis, and autophagy of tumor cells. Currently, there is a lack of comprehensive analysis of MAZ in pan-cancer, and the mechanism of MAZ in hepatocellular carcinoma (HCC) and its association with immunotherapy remains unclear. The expression, prognostic mutation, sCNA, and tumor immunity characteristics of MAZ in 33 types of tumors were analyzed by The Cancer Genome Atlas (TCGA), GEPIA, and TIMER databases. The association of MAZ expression levels with drug sensitivity, immunotherapy, immune checkpoints, and HLA-associated genes was further analyzed. Transwell, CCK-8, wound healing, and flow cytometry verified that MAZ affected the malignant cell behavior of HCC. The signaling pathways and cellular functions affected by MAZ in HCC were revealed by GSEA enrichment analysis. The expression level of MAZ was up-regulated, and the high expression of MAZ indicated a high-risk prognostic factor in most tumors, including ACC, BLCA, KIRP, LIHC, PRAD, SKCM, and THCA (p<0.05). MAZ expression was positively correlated with the sensitivity of most chemotherapy drugs (p<0.05). HLA-DQB2, HLA-H, and most immune checkpoint genes were remarkably up-regulated in the high MAZ expression group (p<0.05). GSEA analysis revealed that MAZ expression was highly correlated with the intracellular immune-related functions and cancer-related signaling pathway, including the B cell receptor signaling pathway, complement activation, humoral immune response, TGF-β signaling pathway, and Wnt signaling pathway. The overexpression of MAZ in HCC cells could promote the abilities of cell proliferation and migration and inhibit tumor cell apoptosis. Our study revealed that MAZ might play a role in promoting the progression of HCC. It was closely related to the tumor microenvironment, immune cell infiltration, and immune escape in pan-cancer. Moreover, this study provides new insights into MAZ as a prognostic marker and potential therapeutic target in HCC.