Abstract PO-005: GATA6 expression is prognostic after surgical resection of pancreatic cancer: results from the ESPAC trials
Authors: Grant Robert C. , Duan Kai , Jackson Richard , Greenhalf William , Costello-Goldring Eithne , Ghaneh Paula , Halloran Christopher , Palmer Daniel , Hackert Thilo , Buchler Markus , Hutchison Shawn , Ramotar Stephanie , Dodd Anna , Wilson Julie , Notta Faiyaz , O'Kane Grainne , Knox Jennifer , Neoptolemos John , Gallinger Steven , Fischer Sandra 
Published: November 2020

Abstract
Introduction No biomarker is clinically available to predict prognosis after surgical resection of pancreatic cancer beyond CA-19-9, a classical tumor marker. GATA6 is a transcription factor necessary for pancreaticogenesis that associates with the major transcriptomic subtypes of pancreatic cancer. In this study, we evaluated the prognostic utility of GATA6 expression in randomised adjuvant chemotherapy trials. Materials and Methods We retrospectively analyzed resection specimens in tissue microarrays from patients who participated in two international randomized phase III trials of adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: ESPAC-3, which compared fluorouracil plus folinic acid with gemcitabine; and ESPAC-4, which compared gemcitabine plus capecitabine with gemcitabine alone. GATA6 expression was measured using immunohistochemistry. Expression levels from 0 to 4 were scored through consensus between two pathologists who were blinded to clinical characteristics and outcome. Concordance on each tissue core was assessed using a weighted kappa score. Overall survival (OS) was assessed using Kaplan-Meier curves and compared between GATA6 expression levels using univariate Cox proportional hazard regression models and multivariate models that adjusted for lymph node status, post-operative CA-19-9, and treatment arms. After an initial analysis of all five levels, expression levels were regrouped into low (0-2) and high (3-4). Our primary objective was to assess for a prognostic association between GATA6 and OS. Secondary analyses considered predictive associations with the addition of capecitabine to gemcitabine using an interaction term, and associations with baseline characteristics using Wilcoxon and Fisher-exact tests. Results: 26 patients from ESPAC-3 and 205 patients from ESPAC-4 were included. 7, 18, 130, 74, and 2 patients had GATA6 expression levels of 0, 1, 2, 3, and 4, respectively. Concordance between pathologists was moderate (weighted kappa 0.41). GATA6 expression was significantly associated with overall survival when regrouped into low (0–2, N=155) and high (3–4, N=76) expression. Low GATA6 expression was associated with shorter OS (median OS 26.1 months, 95% confidence interval (CI) 22.9–30.4 versus 42.4 months, 95% CI 30.2–56.5, univariate hazard ratio (HR) 1.70, 95% CI 1.31–2.41, P=0.002), which persisted after adjustment for potential confounders (multivariate HR 1.57, 95% CI 1.09–2.62, P=0.016). GATA6 expression was not significantly associated with baseline characteristics or predictive of differential benefit from the addition of capecitabine to gemcitabine. Conclusion: Low GATA6 expression is significantly associated with inferior OS after surgical resection of pancreatic cancer. Future research will automate the measurement of GATA6 expression using image analyses.
Citation Format: Robert C. Grant, Kai Duan, Richard Jackson, William Greenhalf, Eithne Costello-Goldring, Paula Ghaneh, Christopher Halloran, Daniel Palmer, Thilo Hackert, Markus Buchler, Shawn Hutchison, Stephanie Ramotar, Anna Dodd, Julie Wilson, Faiyaz Notta, Grainne O'Kane, Jennifer Knox, John Neoptolemos, Steven Gallinger, Sandra Fischer. GATA6 expression is prognostic after surgical resection of pancreatic cancer: results from the ESPAC trials [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-005.