A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection

Autor: Terence M. Williams, Ryan Robb, Mary Dillhoff, Wooil Kwon, Nikhil Sebastian, Adam R. Wolfe, Wendy L. Frankel, Wei Chen, Steve Walston, Patrick Wald, Jin-Young Jang, Amy Webb, Marall Vedaie
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Adam R. Wolfe 1 , * , Patrick Wald 1 , * , Amy Webb 1 , Nikhil Sebastian 1 , Steve Walston 1 , Ryan Robb 1 , Wei Chen 1 , Marall Vedaie 1 , Mary Dillhoff 1 , Wendy L. Frankel 1 , Wooil Kwon 2 , Jin-Young Jang 2 and Terence M. Williams 1 1 The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA 2 Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea * Co-first authors Correspondence to: Terence M. Williams, email: terence.williams@osumc.edu Keywords: pancreatic cancer; miRNA; non-coding RNA; prognostic biomarker; local-regional recurrence Received: November 12, 2019 Accepted: January 29, 2020 Published: March 10, 2020 ABSTRACT Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR ( p = 0.001) and worse OS ( p = 0.034). Two-year OS rates for the high- and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR ( p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate ( p = 0.03) and multivariable analysis ( p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS ( p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.
Databáze: OpenAIRE
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