Journal Article

Cuproptosis related gene PDHB is identified as a biomarker inversely associated with the progression of clear cell renal cell carcinoma

Wang, Zhu, Wang, Hu, Wen, Hongzhuang, Guo, Fengran, Teng, Zhihai, Han, Zhenwei, Yang, Zhan, Xu, Sen, Xu, Chao, Sun, Hao, Wang, Yaxuan, He, Xingyu

2023

Overview

Background Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. Pyruvate dehydrogenase E1 subunit beta (PDHB) is one of the cuproptosis genesand is a nuclear-encoded pyruvate dehydrogenase, which catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We further analyzed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we preliminarily explored the impact of PDHB on ccRCC. Results The expression level of PDHB was lower in tumor tissue compared with normal tissue. Meanwhile, the expression level of PDHB was also lower in high-grade tumors than low-grade tumors. PDHB is positively correlated with prognosis in ccRCC. Furthermore, PDHB may be associated with decreased risk of VHL, PBRM1 and KDM5C mutations. In 786-O cells, copper chloride could promote the expression of cuproptosis genes (DLAT, PDHB and FDX1) and inhibit cell growth. Last but not least, we found that PDHB could inhibit the proliferation and migration of ccRCC cells. Conclusion Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alzheimer's disease / Analysis / Apoptosis / Biological markers / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Carcinoma, Renal cell / Care and treatment / Cell culture / Cell death / Cell migration / Cell proliferation / Clear cell renal cell carcinoma / Clear cell-type renal cell carcinoma / Coenzyme A / Copper / Copper chloride / Cuproptosis / Development and progression / Enzymes / Gene expression / Genes / Health aspects / Health Promotion and Disease Prevention / Kidney cancer / Kinases / Medical prognosis / Medicine/Public Health / Membranes / Metastases / Mutation / Oncology / Patients / PDHB / Pyruvic acid / Software packages / Surgical Oncology / Thiols / Tumor immune microenvironment / Tumors