GATA6 and Keratin5 Expression Profile is a Reliable Biomarker for Prediction of Improved Survival with Adjuvant Chemotherapy after Surgical Resection in PDAC

Abstract

Introduction: GATA6 expression is a surrogate marker for classical-type PDAC that can be utilized as a prognostic tool. Our aim was to evaluate GATA6 and Keratin5 (KT5) expression as biomarkers in selecting patients who would benefit most from adjuvant therapy (AT) after surgical resection. Methods: 76 patients who underwent upfront resection at Johns Hopkins Hospital (2015-2018) were selected. Immunohistochemistry staining for GATA6 and KT5 protein expression was performed on archived primary tumor specimens. Results: Among 76 patients, 40(52.6%) patients had high GATA6 expression; 36(47.3%) had low GATA6 with no significant differences in clinicopathologic characteristics. Patients with low GATA6 expression had median overall survival (mOS=17.4 months), significantly lower than high expression (25.1months)(P=0.033). GATA6 and Keratin5 staining was concordant in 55(72.3%) cases [GATA6 High/KT5 Low(n=31);GATA6 Low/KT5 High(n=24)]. To evaluate the role of GATA6 and KT5 expression in predicting AT benefit, we stratified by expression status. In low GATA6, receiving AT was associated with improved mOS (20.3 months) compared to 6.5 months in those not receiving it (P<0.001);no significant difference in high GATA6 group. In high KT5 group, receiving AT was associated with mOS (26.8 months) compared to 7.4mo in those not receiving it (P<0.001);no significant difference in low KT5 group. Utilizing dual marker expression, patients with GATA6 Low/KT5 High profile exhibited improved survival with adjuvant therapy; those with GATA6 High/KT5 Low showed no benefit (Figure1). Conclusion: Dual GATA6/KT5 expression is a reliable biomarker to predict benefit from AT after surgical resection. AT in patients with low GATA6 and high KT5 expression is associated with improved survival.