Alteration of TGF-β signaling pathway predicts worse prognosis in pancreatic ductal adenocarcinoma.

Abstract

e13006 Background: Transforming growth factor beta (TGF-β) signaling pathway is one of the core pathways involved in tumor initiation and progression. The prognostic value of TGF-β pathway genes as a functionally related group in pancreatic ductal adenocarcinoma (PDAC) is rarely studied. Methods: 72 PDAC patients who underwent surgery between November 30, 2015 and September 13, 2017 in West China Hospital, Sichuan University were identified and included in this study. Whole-exome sequencing (WES) or targeted next-generation sequencing was performed with tumor tissue from all the participants. Clinical data was retrospectively collected. Clinicopathologic characteristics and overall survival (OS) were analyzed. Results: Genetic alterations were detected in 71 patients (98.6%). While 1 patient (1.4%) had only one genetic alteration, 33 patients (45.8%) had 2-4 genetic alterations and 37 patients (51.4%) had ≥5 genetic alterations. Overall, 25 patients (34.7%) with alteration of TGF-β pathway and 47 patients (65.3%) with wild type of TGF-β pathway were identified as TGF-βm+ group and TGF-βm- group respectively. Mutation of TGF-β pathway was independently associated with inferior OS in present cohort (HR, 2.22; 95% CI, 1.05-4.70; P = 0.04), adjusted for tumor stage, metastasis, surgery method and comorbidity. Subgroup analysis showed that patients with mutation of TGF-β pathway had shorter OS after radical surgery (HR, 3.25, 95% CI: 1.01–10.49; P = 0.04). While in the subgroup of patients who underwent palliative surgery, OS was not statistically different (HR, 0.93, 95% CI: 0.41–2.09; P = 0.86). Conclusions: Inferior prognosis was observed in PDACs with mutations of TGF-β pathway. Genomic information could help screen out patients at risk after surgery and adjuvant therapy might benefit this subgroup of PDACs.