Research Papers:
Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma
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Abstract
Daisuke Matsui1, Ali H. Zaidi1, Samantha A. Martin1, Ashten N. Omstead1, Juliann E. Kosovec1, Luai Huleihel2, Lindsey T. Saldin2, Christina DiCarlo3, Jan F. Silverman3, Toshitaka Hoppo1, Gene G. Finley4, Stephen F. Badylak2, Ronan J. Kelly5, Blair A. Jobe1
1Esophageal and Lung Institute, Allegheny Health Network, Pittsburgh, PA, USA
2McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
3Department of Pathology and Laboratory Medicine, Allegheny Health Network, Pittsburgh, PA, USA
4Department of Medicine, Division of Hematology and Oncology, Allegheny Health Network, Pittsburgh, PA, USA
5Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Correspondence to:
Blair A. Jobe, email: [email protected]
Keywords: esophageal adenocarcinoma, prognostic marker, miRNA, miR-652-5p, miR-7-2-3p
Received: September 07, 2016 Accepted: September 26, 2016 Published: October 24, 2016
ABSTRACT
Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC.
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