Discovering Cure Hub Genes of Chromophobe Cell Renal Carcinoma Using weighted gene co-expression network analysis (WGCNA) and the Cure Defective Models

Renal cell carcinoma (RCC) is a prevalent and aggressive tumor of the urinary system with limited treatment success and poor patient outcomes. However, some patients exhibit long-term symptom relief and are considered cured after successful treatment. This study explores the genetic and pathway mechanisms underlying RCC cure for the first time, utilizing a survival model called the 3-parameter defective Gompertz cure model. The study methodology involved two main steps: Firstly, employing Weighted Gene Co-expression Network Analysis (WGCNA) for gene network analysis, which identified six key modules associated with different aspects of cancer progression and survival. Hub genes, pivotal in cellular interactions, were pinpointed through network analysis. Secondly, the 3-parameter defective Gompertz model was utilized to identify therapeutic genes linked to successful treatment outcomes (CSRGs) in RCC. These genes were then compared with genes associated with patient survival (SRGs) using a cox model. The study found ten hub genes commonly identified by both the defective 3-parameter Gompertz and Cox models, with six genes (NCAPG, TTK, DLGAP5, TOP2A, BUB1B, and BUB1) showing strong predictive values. Moreover, six hub genes (TTK, KIF20A, DLGAP5, BUB1, AURKB, and CDC45) were highlighted by the defective Gompertz model as significantly impacting cure when expressed at high levels. Targeting these hub genes may hold promise for improving RCC treatment outcomes and prognosis prediction. Overall, this study provides valuable insights into the molecular mechanisms of RCC and underscores the potential of the defective 3-parameter Gompertz model in guiding targeted therapeutic approaches.