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
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.
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.
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.
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.
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.
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.