Moffitt’s Basal-Like Gene Signature Associated With Poor Survival in Pancreatic Cancer

The Moffitt gene sets of locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) identified a poor prognostic group, according to a study presented at the 2018 AACR Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston, Massachusetts.¹

Though RNA signatures have been studied in PDAC, a clinically meaningful tool has not yet been developed. The purpose of the COMPASS trial was to use molecular characterization of patients with PDAC prior to treatment to identify predictive and prognostic biomarkers.

The COMPASS trial included 103 patients with locally advanced or metastatic PDAC with at least 5 months of follow-up. Core biopsies were used for whole-exome sequencing and RNA-seq prior to treatment initiation. The Collisson, Moffitt, and Baily gene sets were used to identify patient RNA subtypes. In situ hybridization of GATA6 was also analyzed and scored as high (≥ 2) or low (0 to 1).

There were no differences in survival between subsets identified by either Collison’s or Bailey’s gene signatures. Collison’s gene signatures classified 51% of samples as quasimesenchyma, 39% as classical, and 10% as exocrine. Bailey’s gene signatures classified 53% of samples as squamous, 33% as progenitor, 6% as ADEX, and 8% as immunogenic.

The Moffitt gene signatures categorized 77% of tumors as classical and 23% as basal-like. Improved survival was significantly associated with Moffitt’s classical gene signature, with a median of 8.48 months compared with 5.85 months for basal-like tumors (hazard ratio, 0.56; 95% CI, 0.32-0.94; P = .02). There were no differences in baseline characteristics between the classical and basal-like groups, except that all classical cases had locally advanced disease and more patients with the classical signature had type 2 diabetes mellitus.

High GATA6 scores demonstrated strong correlation with Moffitt’s classical gene signature, and low GATA6 scores correlated with the basal-like signature.

The authors stated that these results suggest that “the Moffitt basal-like gene set clearly identifies a poor prognostic patient group.” They note that the GATA6 in situ hybridization is a test that “can reliably identify this population and may provide a biomarker for clinical trial design.”

Reference

1. O’Kane G, Jang G-H, Dodd A, et al. RNA profiling and the impact of current classifiers on survival in patients receiving combination chemotherapy on the COMPASS trial. Presented at: AACR Pancreatic Cancer: Advances in Science and Clinical Care; Boston, Massachusetts, September 21-24, 2018. Abstract A003.