Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2024; 16(1): 144-181
Published online Jan 15, 2024. doi: 10.4251/wjgo.v16.i1.144
Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit β in human cancer
Yao Rong, Song-Hua Liu, Ming-Zheng Tang, Zhi-Hang Wu, Guo-Rong Ma, Xiao-Feng Li, Hui Cai
Yao Rong, Song-Hua Liu, Ming-Zheng Tang, Zhi-Hang Wu, Guo-Rong Ma, Xiao-Feng Li, First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Yao Rong, Song-Hua Liu, Ming-Zheng Tang, Hui Cai, General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Yao Rong, Ming-Zheng Tang, Hui Cai, Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Yao Rong, Ming-Zheng Tang, Hui Cai, NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Co-first authors: Yao Rong and Song-Hua Liu.
Author contributions: Rong Y and Cai H conceived and designed the study; Rong Y wrote and revised the manuscript, and Rong Y and Liu SH jointly completed the methodology section, Rong Y mainly performed the operation of related software and the production of charts related to bioinformatics analysis, and Liu SH mainly carried out bioinformatics analysis and statistical analysis of the experimental data; Rong Y, Liu SH and Tang MZ jointly completed quantitative reverse transcription PCR, western blot, and cell function experiments; Rong Y and Liu SH made outstanding contributions to the manuscript revision process, with Rong Y rewriting the manuscript content and Rong Y and Liu SH correcting all figures; Rong Y and Liu SH contributed equally to this article. Wu ZH, Ma GR, Li XF performed all the data collection and analysis, and generated the charts; all authors read and approved the final manuscript.
Supported by The 2021 Central-Guided Local Science and Technology Development Fund; Lanzhou COVID-19 Prevention and Control Technology Research Project, No. 2020-XG-1; Gansu Province Outstanding Graduate Student "Innovation Star" Project, No. 2022CXZX-748, No. 2022CXZX-746.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to report regarding the present study.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
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: Hui Cai, PhD, Doctor, General Surgery Clinical Medical Center, Gansu Provincial Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China. caialonteam@163.com
Received: August 19, 2023
Peer-review started: August 19, 2023
First decision: October 18, 2023
Revised: October 28, 2023
Accepted: December 1, 2023
Article in press: December 1, 2023
Published online: January 15, 2024
Abstract
BACKGROUND

The pyruvate dehydrogenase E1 subunit β (PDHB) gene which regulates energy metabolism is located in mitochondria. However, few studies have elucidated the role and mechanism of PDHB in different cancers.

AIM

To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer. In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.

METHODS

Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas (TCGA) database. Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases. Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients. The correlation between PDHB and receiver operating characteristic diagnostic curve, clinicopathological staging, somatic mutation, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation, and drug susceptibility in pan-cancer was also analyzed. Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment, as well as the co-expression analysis of PDHB and immune checkpoint (ICP) genes. The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing, and the functional enrichment analysis of PDHB-related genes was performed. The study also validated the level of mRNA or protein expression of PDHB in several cancers. Finally, in vitro experiments verified the regulatory effect of PDHB on the proliferation, migration, and invasion of liver cancer.

RESULTS

PDHB was significantly and differently expressed in most cancers. PDHB was significantly associated with prognosis in patients with a wide range of cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, breast invasive carcinoma, and brain lower grade glioma. In some cancers, PDHB expression was clearly associated with gene mutations, clinicopathological stages, and expression of TMB, MSI, and ICP genes. The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment. In addition, single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells. This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation, migration, and invasion functions of hepatoma cells.

CONCLUSION

As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

Keywords: Cuprotosis, Pyruvate dehydrogenase E1 subunit β, Pan-cancer, Prognosis, Liver cancer

Core Tip: In this study, the multi-faceted correlation between pyruvate dehydrogenase E1 subunit β (PDHB) expression and pan-cancer development was comprehensively studied using bioinformatics analysis. The regulatory effect of PDHB on the malignant phenotype of liver cancer was specifically verified by cell function experiments. Our research suggests that PDHB is closely related to tumor diagnosis, patient prognosis, and tumor immune microenvironment in a variety of tumors. In vitro experimental results showed that overexpressed PDHB could promote the proliferation, migration, and invasion ability of hepatoma cells. PDHB could be a new tumor marker and a potential target for tumor-targeted therapies.