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:
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.
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
Research background

Cancer remains the most serious public health problem worldwide, with a high mortality rate. The best prognosis of cancer patients benefits from early detection and timely treatment. Therefore, early diagnosis and treatment are particularly important, and the discovery of new diagnostic and prognostic markers in addition to potential molecular therapeutic targets are essential.

Research motivation

Pyruvate dehydrogenase E1 subunit β (PDHB) is closely associated with the regulation of cancer metabolism and is significantly differentially expressed in multiple cancers. However, there is a lack of reports exploring the role of PDHB in cancer from multiple perspectives, and we expect to provide evidence for the use of PDHB as a potential biomarker for cancers, predominantly liver cancer.

Research objectives

In this study, we used bioinformatics methods and cell function experiments to investigate the diagnostic and prognostic value and tumor immune relevance of PDHB in pan-cancer, as well as its biological regulation in liver cancer.

Research methods

PDHB-related pan-cancer data were obtained from The Cancer Genome Atlas (TCGA) database, and gene expression profiles of PDHB were explored based on TCGA and Genotypic Tissue Expression Dataset databases. The correlation between PDHB and survival was analyzed using Cox regression analysis and Kaplan-Meier methods. Receiver operating characteristic diagnosis, tumor staging, mutation assessment, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation and drug sensitivity were also assessed for PDHB. Correlation of PDHB with immune cell infiltration and tumor chemotactic environment, and co-expression analysis of PDHB with immune checkpoint (ICP) genes were analyzed using different algorithms. The expression and functional phenotypes of PDHB in tumor single cells were investigated by single-cell sequencing, and enrichment analysis of the potential oncogenic functions of PDHB was performed. The expression of mRNA or protein levels of PDHB in several cancers was validated. Finally, the regulatory effect of PDHB on the proliferation, migration and invasion of liver cancer was verified.

Research results

PDHB was clearly differentially expressed in most cancers. PDHB was significantly associated with the prognosis of patients with a variety of cancers. In some cancers, PDHB expression was clearly correlated with gene mutation, pathological stage, TMB, MSI, and ICP gene expression. The expression of PDHB was closely related to the infiltration of various immune cells in the immune microenvironment and the regulation of tumor chemotactic environment. In addition, single-cell sequencing results showed that PDHB was associated with different biological phenotypes of single cells in a variety of cancers. The present study further demonstrated that downregulation of PDHB expression inhibited the proliferation, migration and invasion of hepatoma cells.

Research conclusions

PDHB may be a novel cancer marker with potential value in tumor diagnosis, prognosis prediction, immunomodulation, and liver cancer-targeted therapy.

Research perspectives

The role of PDHB in specific types of cancer should be further investigated and the mechanisms by which PDHB is associated with cuproptosis in cancer require further examination.