Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 475-492
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.475
Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma
Hong-Mei Wu, Yuan-Yuan Huang, Yu-Qiu Xu, Wei-Lai Xiang, Chang Yang, Ru-Yuan Liu, Di Li, Xue-Feng Guo, Zheng-Bao Zhang, Chun-Hua Bei, Sheng-Kui Tan, Xiao-Nian Zhu
Hong-Mei Wu, Yuan-Yuan Huang, Yu-Qiu Xu, Wei-Lai Xiang, Chang Yang, Ru-Yuan Liu, Di Li, Xue-Feng Guo, Zheng-Bao Zhang, Chun-Hua Bei, Sheng-Kui Tan, Xiao-Nian Zhu, Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China
Co-first authors: Hong-Mei Wu and Yuan-Yuan Huang.
Author contributions: Wu HM, Huang YY, and Zhu XN conceived, designed, and wrote the original draft; Wu HM, Xu YQ, Xiang WL, Yang C, Liu RY, Li D, and Guo XF performed the formal analysis; Zhang ZB, Bei CH, and Tan SK conducted the methodology; Bei CH, Tan SK, and Zhu XN were responsible for the conceptualization, writing, review and editing; and all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82060621, 82060607, and 82260664; Natural Science Foundation of Guangxi Province, No. 2020GXNSFDA297010 and 2020GXNSFAA297142; and Key Science and Technology Research and Development Program Project of Guangxi, No. AB22035017.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Guilin Medical University (No. GLMC2020045).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Publicly available datasets were analyzed in this study. No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Nian Zhu, MD, Professor, Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, No. 1 Zhiyuan Road, Guilin 541199, Guangxi Zhuang Autonomous Region, China. zhuxiaonian0403@163.com
Received: October 17, 2023
Peer-review started: October 17, 2023
First decision: December 5, 2023
Revised: December 10, 2023
Accepted: January 8, 2024
Article in press: January 8, 2024
Published online: February 15, 2024
Processing time: 107 Days and 17.4 Hours
Abstract
BACKGROUND

B56ε 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 B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear.

AIM

To analyze B56ε 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 B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε 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 B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells.

RESULTS

In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε 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 B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε 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 B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells.

CONCLUSION

B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Keywords: B56ε; Prognosis; Tumor microenvironment; Immune infiltration; Immunotherapy; Hepatocellular carcinoma

Core Tip: The expression of protein phosphatase 2A (PP2A) subunit B56ε is up-regulated in most tumors, and its high expression is a risk factor for adrenocortical cancer, hepatocellular carcinoma (HCC), pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma. B56ε expression levels correlate with immune cells, immune checkpoint genes, human leukocyte antigen-related genes, and the sensitivity of chemotherapy drugs. In HCC, B56ε expression is related to the cancer pathway. Knockdown of B56ε expression in HCC cells can inhibit the proliferation, migration and invasion capacity of tumor cells. Our study supports PP2A subunit B56ε as a prognostic marker and potential therapeutic target for HCC.