Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

Abstract

Background Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. PDHB is one of the genes responsible for cuproptosis and is a nuclear encoded pyruvate dehydrogenase, an enzyme that catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in renal clear cell carcinoma remains unclear. Methods We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We analysed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we explored the impact of overexpressed PDHB on renal clear cell carcinoma. Results PDHB is lowly expressed in tumor tissue and reduced in high-grade tumors. Highly expressed PDHB has a better prognosis in ccRCC. In ccRCC, low PDHB expression may be associated with higher VHL, PBRM1 and KDM5C mutations. Addition of copper chloride to the 786-O cell line resulted in inhibition of cell growth and increased expression of the cuproptosis genes DLAT, PDHB and FDX1. Finally, the experiments verified that overexpression of PDHB inhibited the proliferation and migration of ccRCC cells. Conclusion Our results demonstrate that elevated PDHB expression inhibits the proliferation, migration and invasion of renal clear cell carcinoma cells, improves the prognosis of renal cancer patients and may provide a new therapeutic strategy for patients with advanced renal cancer.