Published online Jan 15, 2024. doi: 10.4251/wjgo.v16.i1.144
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
Processing time: 144 Days and 15.9 Hours
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.
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.
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.
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.
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.
PDHB may be a novel cancer marker with potential value in tumor diagnosis, prognosis prediction, immunomodulation, and liver cancer-targeted therapy.
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.