Abstract 4939: Alteration of TGFB signaling pathway predicts worse prognosis in pancreatic ductal adenocarcinoma

Abstract

Abstract Background: For pancreatic ductal adenocarcinoma (PDAC), a reliable and practical prognostic biomarker is still in unmet needs. Transforming growth factor beta (TGFB) signaling pathway is one of the core pathways involved in tumor initiation and progression via canonical and non-canonical pathway. The prognostic value of TGFB pathway genes as a functionally related group in 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 primary tumors. Clinical data was retrospectively collected. Clinicopathologic characteristics and overall survival were analyzed.Results: Genetic alterations were detected in 70 patients (97.2%). While 1 patient (1.4%) had only one genetic alteration, 28 patients (38.9%) had 2-4 genetic alterations and 43 patients (59.7%) had ≥5 genetic alterations. Overall, 25 patients (34.7%) with alteration of TGFB pathway and 47 patients (65.3%) with wild type of TGFB pathway were identified as TGFBm+ group and TGFBm- group respectively. TGFBm+ group had worse overall survival (HR, 1.875, 95% CI: 1.06-4.72; P = 0.04), especially in patients who had radical surgery (HR, 3.11, 95% CI: 1.11-20.3; P = 0.04). While in the subgroup of patients who underwent palliative surgery, OS was not statistically different (HR, 0.93, 95% CI: 0.42-2.04; P = 0.85). Subgroup analysis showed that overall survival hazard ratio favored participants with wild type of TGFB pathway in patients with ECOG performance score >1, abnormal CA199, without metastasis, stage I to II and patients who accepted radical surgery.Conclusion: Alteration of TGFB pathway genes is prevalent in PDAC. Inferior prognosis was observed in PDACs with mutations of TGFB pathway. TGFB signaling might play different role in different tumor stages, which is consistent with previous report about paradoxical effect of TGFB pathway. Genomic sequencing could help screen out patients at risk after surgery and adjuvant therapy might benefit this subgroup of PDACs. Note: This abstract was not presented at the meeting. Citation Format: Mao Li, Ang Li, Xiaochen Zhao, Shengzhong Hou, Shan Lu, Yu Mou, Xubao Liu, Dan Cao, Shangli Cai, Bole Tian. Alteration of TGFB signaling pathway predicts worse prognosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4939.