Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Metastatic disease causes most deaths. We investigated the association between ATP4A gene status and survival following nephrectomy. ATP4A encodes H+/K+ ATPase, targeted by proton pump inhibitors (PPIs). We also examined how perioperative use of these drugs affects cancer progression post-surgery.
Using a publicly available database, we employed in silico analysis to investigate the association between the ATP4A gene and recurrence-free survival and overall survival. After receiving institutional review board approval from the University of Texas-MD Anderson Cancer Center (#2020-0380), we conducted a retrospective analysis to investigate the association between perioperative PPIs use and progression of nonmetastatic ccRCC. We performed a propensity score analysis and utilized inverse probability of treatment weighting to balance potential discrepancies between exposure groups. A Cox proportional hazards model, weighted by inverse probability of treatment weighting, was subsequently fitted for multivariable analysis.
ATP4A gene expression analysis showed that high tumor levels were associated with a significant reduction in overall survival. The analysis included a total of 1775 patients with ccRCC. After propensity matching, the analysis revealed that the use of perioperative PPIs was not independently associated with a worse oncological prognosis following nephrectomies.
Elevated ATP4A gene expression correlates with reduced survival, while perioperative PPI use shows no significant impact on survival outcomes.
Cancer medicine. 2026 Mar [Epub]
Nicolas Cortes-Mejia, Ryan Wong, Holger K Eltzschig, Sergio M Moreno-Lopez, Diana Bejarano-Ramirez, Huang Huang, Juan P Cata
Department of Surgery, Wyckoff Heights Medical Center, New York City, New York, USA., Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, Texas, USA., Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Medical School UT Health, Houston, Texas, USA., School of Medicine, Universidad de Los Andes, Bogota, Colombia., Transplant and Hepatobiliary Surgery Department, Fundación Santa Fe de Bogotá, Bogotá, Colombia., Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.