Journal
CLINICAL CANCER RESEARCH
Volume 27, Issue 1, Pages 150-157Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-2831
Keywords
-
Categories
Funding
- Terry Fox Research Institute [1078]
- Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative)
- Genome British Columbia [B20POG]
- VGH/UBC Hospital Foundation
- MSFHR Health Professional-Investigator Award
- VCHRI Investigator Award
- Pancreatic Cancer Canada
Ask authors/readers for more resources
RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) using multiple classification tools revealed 12% of tumors with inconsistent subtype calls, showing intermediate survival and molecular characteristics. It is proposed to further investigate the non-binary nature of PDAC subtypes for future clinical practice integration.
Purpose: RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. Classical and basal-like PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. Experimental Design: Sequencing data for 574 PDAC tumors was obtained from prospective trials and retrospective public databases. Six published PDAC subtyping strategies (Moffitt regression tools, clustering-based Moffitt, Collisson, Bailey, and Karasinska subtypes) were used on each sample, and results were tested for subtype call consistency and association with survival. Results: Basal-like and classical subtype calls were concordant in 88% of patient samples, and survival outcomes were significantly different (P < 0.05) between prognostic subtypes. Twelve percent of tumors had subtype-discordant calls across the different methods, showing intermediate survival in univariate and multivariate survival analyses. Transcriptional profiles compatible with that of a hybrid subtype signature were observed for subtype-discordant tumors, in which classical and basal-like genes were concomitantly expressed. Subtype-discordant tumors showed intermediate molecular characteristics, including subtyping gene expression (P < 0.0001) and mutant KRAS allelic imbalance (P < 0.001). Conclusions: Nearly 1 in 6 patients with PDAC have tumors that fail to reliably fall into the classical or basal-like PDAC subtype categories, based on two regression tools aimed toward clinical practice. Rather, these patient tumors show intermediate prognostic and molecular traits. We propose close consideration of the non-binary nature of PDAC subtypes for future incorporation of subtyping into clinical practice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available