Comprehensive analyses of nuclear mitochondria‐related genes in the molecular features, immune infiltration, and drug sensitivity of clear cell renal cell carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most common urological diseases and the most common subtype of renal cell carcinoma. Nuclear mitochondria‐related genes (MTRGs) play an essential role in cancer, but their effect on ccRCC has not been clarified. This work aimed to investigate the role of nuclear MTRGs in ccRCC. Methods We collected nuclear MTRGs from the MITOMAP database and obtained the ccRCC profile from the TCGA database. Gene expression validation came from the GEO database. The ccRCC subtypes were determined by unsupervised clustering analysis based on the nuclear MTRGs. Immune scores were computed using the EPIC algorithm. The drug sensitivity scores were calculated using GDSC resources. A nomogram explored the diagnostic value of the nuclear MTRGs. Results In total, 11 nuclear MTRGs were identified as both related to prognosis and differentially expressed in ccRCC, showing a significant positive correlation with CD274 expression. We determined two subtypes of ccRCC based on these genes and found remarkable differences in survival status, immune infiltration, mutation landscape, and drug sensitivity between the two subtypes. The high‐MTRG group had a better prognosis and a lower tumor stage than the low‐MTRG group. Immune checkpoint blockade therapy was more effective for the high‐MTRG group. A nomogram based on the nuclear MTRGs concluded that patients with a higher score had poorer survival. SUCLA2 (succinate‐CoA ligase ADP‐forming subunit beta) was identified as the hub gene linked to ccRCC. High SUCLA2 expression showed a correlation with better survival and a negative correlation with the tumor mutation burden in ccRCC. Pan‐cancer analysis revealed wide‐ranging roles for SUCLA2 across human tumors. Conclusions Nuclear MTRGs play vital roles in determining the molecular features, immune infiltration, and drug sensitivity of ccRCC. High levels of nuclear MTRGs may indicate a better prognosis for patients with ccRCC. SUCLA2 is a representative nuclear MTRG and may serve as a protective biomarker in ccRCC. Our study provides therapeutic guidance and potential biomarkers for ccRCC patients, and contributes to the advancement of precision medicine.