PMID- 38425404 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240308 IS - 1948-5204 (Print) IS - 1948-5204 (Electronic) VI - 16 IP - 2 DP - 2024 Feb 15 TI - Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56epsilon in pan-cancer and its role and mechanism in hepatocellular carcinoma. PG - 475-492 LID - 10.4251/wjgo.v16.i2.475 [doi] AB - BACKGROUND: B56epsilon 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 B56epsilon in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56epsilon 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 B56epsilon expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56epsilon 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 B56epsilon in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56epsilon interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56epsilon expression was upregulated, and high B56epsilon expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56epsilon 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 B56epsilon expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56epsilon 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 B56epsilon expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56epsilon expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56epsilon is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56epsilon plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC. CI - (c)The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved. FAU - Wu, Hong-Mei AU - Wu HM AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Huang, Yuan-Yuan AU - Huang YY AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Xu, Yu-Qiu AU - Xu YQ AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Xiang, Wei-Lai AU - Xiang WL AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Yang, Chang AU - Yang C AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Liu, Ru-Yuan AU - Liu RY AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Li, Di AU - Li D AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Guo, Xue-Feng AU - Guo XF AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Zhang, Zheng-Bao AU - Zhang ZB AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Bei, Chun-Hua AU - Bei CH AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Tan, Sheng-Kui AU - Tan SK AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. FAU - Zhu, Xiao-Nian AU - Zhu XN AD - Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China. zhuxiaonian0403@163.com. LA - eng PT - Journal Article PL - China TA - World J Gastrointest Oncol JT - World journal of gastrointestinal oncology JID - 101532470 PMC - PMC10900161 OTO - NOTNLM OT - B56epsilon OT - Hepatocellular carcinoma OT - Immune infiltration OT - Immunotherapy OT - Prognosis OT - Tumor microenvironment COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. EDAT- 2024/03/01 06:44 MHDA- 2024/03/01 06:45 PMCR- 2024/02/15 CRDT- 2024/03/01 03:44 PHST- 2023/10/17 00:00 [received] PHST- 2023/12/10 00:00 [revised] PHST- 2024/01/08 00:00 [accepted] PHST- 2024/03/01 06:45 [medline] PHST- 2024/03/01 06:44 [pubmed] PHST- 2024/03/01 03:44 [entrez] PHST- 2024/02/15 00:00 [pmc-release] AID - 10.4251/wjgo.v16.i2.475 [doi] PST - ppublish SO - World J Gastrointest Oncol. 2024 Feb 15;16(2):475-492. doi: 10.4251/wjgo.v16.i2.475.