GATA6 amplification is associated with improved survival in TP53-mutated unresectable pancreatic cancer

Abstract

Abstract Objectives: GATA6 expression has been recently recognized as a favorable prognostic marker of pancreatic cancer whereas TP53 is recognized as a poor prognostic marker. We evaluated treatment outcomes by genetic alterations in TP53 and GATA6 to determine the prognostic and predictive impact of co-alterations. Methods A single institution retrospective analysis was performed on patients diagnosed with PDAC between 2014 to 2023. TP53 genotype and GATA6 amplification status were included in an analysis of overall survival (OS) and progression free survival (PFS). Previously published patient-derived organoids were used to investigate correlation between genetic status and drug sensitivity. Results Patients with TP53 mutations had worse OS compared to the wild type TP53 population. In general, patients with GATA6 amplification had better OS and a trend towards better PFS than the non-amplified population. Among patients with a TP53 mutation, patients with GATA6 co-alteration had longer OS compared to those who were not GATA6 amplified. In contrast, among patients who were TP53 wild type, the presence or absence of a GATA6 amplification did not impact OS or PFS. GATA6 genotype was not associated chemotherapy drug response in an organoid pharmacotyping model. Conclusions We found that GATA6 amplification appeared to attenuate poor prognosis observed in TP53-mutant patients regardless of the type of standard chemotherapy received, suggesting the GATA6 amplification is a prognostic biomarker but not a predictive biomarker of standard-of-care chemotherapy.