Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56 in pan-cancer and its role and mechanism in hepatocellular carcinoma

BACKGROUND B56 epsilon is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56 epsilon in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM To analyze B56 epsilon in pan-cancer, and explore its role and mechanism in HCC. METHODS The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56 epsilon expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56 epsilon expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56 epsilon in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56 epsilon interference on the malignant behavior of HCC cells. RESULTS In most tumors, B56 epsilon expression was upregulated, and high B56 epsilon expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56 epsilon expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56 epsilon expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56 epsilon was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56 epsilon expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56 epsilon expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION B56 epsilon is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56 epsilon plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.