SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases

摘要

IntroductionDorsophiliaprotein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway andSMAD4gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM). MethodsBetween 2005 and 2015, all patients with knownSMAD4mutation status who underwent resection of CLM were identified. Patients withSMAD4mutation were compared to those withSMAD4wild type. Next, the prognostic value ofSMAD4mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. ResultsOf 278 patients, 37 (13%) wereSMAD4mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse inSMAD4-mutant patients compared toSMAD4wild type (OS rate at 3 years, 62% vs. 82%;P?