Potential value of mitochondrial regulatory pathways in the clinical application of clear cell renal cell carcinoma: a machine learning-based study

J Cancer Res Clin Oncol. 2023 Dec;149(19):17015-17026. doi: 10.1007/s00432-023-05393-8. Epub 2023 Sep 25.

Abstract

Background: Renal clear cell carcinoma (RCC) is a common cancer in urinary system with increasing incidence. At present, targeted therapy and immunotherapy are the main therapeutic programs in clinical therapy. To develop novel drugs and provide new ideas for clinical therapy, the identification of potential ccRCC subtypes and potential target genes or pathways has become a current research focus.

Aim: The aim of this study was to explore the underlying mechanisms of mitochondrial function in ccRCC. This regulatory pathway is closely related to tumor development and metastasis in ccRCC patients, and their abnormal changes may affect the prognosis of cancer patients. Therefore, we decided to construct a prognostic model of ccRCC patients based on mitochondrial regulatory genes, aiming to provide new methods and ideas for clinical therapy.

Result: The 5-year survival prediction model based on iterative LASSO reached 0.746, and the cox model based on coxph reached C-index = 0.77, integrated c/D AUC = 0.61, and integrated brier score = 0.14. The rsf model based on randomForestSRC was built with C-index = 0.82, integrated c/D AUC = 0.69, and integrated brier score = 0.11. The results show that mitochondrial regulatory pathway is a potential target pathway for clinical therapy of ccRCC, which can provide guidelines for clinical targeted therapy, immunotherapy and other first-line therapy.

Keywords: Bioinformatics; Clear cell renal cell carcinoma; Immunotherapy; Machine learning; Mitochondria; Prognostic model; Target therapy.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / therapy
  • Humans
  • Immunotherapy
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / therapy
  • Machine Learning
  • Mitochondria / genetics
  • Prognosis