Purity Independent Subtyping of Tumors (PurIST), A Clinically Robust, Single-sample Classifier for Tumor Subtyping in Pancreatic Cancer.

TitlePurity Independent Subtyping of Tumors (PurIST), A Clinically Robust, Single-sample Classifier for Tumor Subtyping in Pancreatic Cancer.
Publication TypeJournal Article
Year of Publication2020
AuthorsRashid, Naim U., Xianlu L. Peng, Chong Jin, Richard A. Moffitt, Keith E. Volmar, Brian A. Belt, Roheena Z. Panni, Timothy M. Nywening, Silvia G. Herrera, Kristin J. Moore, Sarah G. Hennessey, Ashley B. Morrison, Ryan Kawalerski, Apoorve Nayyar, Audrey E. Chang, Benjamin Schmidt, Hong Jin Kim, David C. Linehan, and Jen Jen Yeh
JournalClin Cancer Res
Volume26
Issue1
Pagination82-92
Date Published2020 01 01
ISSN1557-3265
KeywordsBiomarkers, Tumor, Clinical Trials as Topic, Computational Biology, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Molecular Typing, Pancreatic Neoplasms, Survival Rate, Treatment Outcome
Abstract

PURPOSE: Molecular subtyping for pancreatic cancer has made substantial progress in recent years, facilitating the optimization of existing therapeutic approaches to improve clinical outcomes in pancreatic cancer. With advances in treatment combinations and choices, it is becoming increasingly important to determine ways to place patients on the best therapies upfront. Although various molecular subtyping systems for pancreatic cancer have been proposed, consensus regarding proposed subtypes, as well as their relative clinical utility, remains largely unknown and presents a natural barrier to wider clinical adoption.EXPERIMENTAL DESIGN: We assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a single-sample classifier (SSC) using penalized logistic regression based on the most robust and replicable schema.RESULTS: We demonstrate that a tumor-intrinsic two-subtype schema is most robust, replicable, and clinically relevant. We developed Purity Independent Subtyping of Tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX.CONCLUSIONS: The flexibility and utility of PurIST on low-input samples such as tumor biopsies allows it to be used at the time of diagnosis to facilitate the choice of effective therapies for patients with pancreatic ductal adenocarcinoma and should be considered in the context of future clinical trials.

DOI10.1158/1078-0432.CCR-19-1467
Alternate JournalClin Cancer Res
Original PublicationPurity independent subtyping of tumors (PurIST), a clinically robust, single-sample classifier for tumor subtyping in pancreatic cancer.
PubMed ID31754050
PubMed Central IDPMC6942634
Grant ListU24 CA211000 / CA / NCI NIH HHS / United States
T32 CA009621 / CA / NCI NIH HHS / United States
R01 CA199064 / CA / NCI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
R01 CA168863 / CA / NCI NIH HHS / United States