Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 21, 2011; 17(35): 3976-3985
Published online Sep 21, 2011. doi: 10.3748/wjg.v17.i35.3976
MicroRNAs as a potential prognostic factor in gastric cancer
Baruch Brenner, Moshe B Hoshen, Ofer Purim, Miriam Ben David, Karin Ashkenazi, Gideon Marshak, Yulia Kundel, Ronen Brenner, Sara Morgenstern, Marisa Halpern, Nitzan Rosenfeld, Ayelet Chajut, Yaron Niv, Michal Kushnir
Baruch Brenner, Ofer Purim, Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel
Baruch Brenner, Ofer Purim, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Moshe B Hoshen, Miriam Ben David, Karin Ashkenazi, Ayelet Chajut, Michal Kushnir, Rosetta Genomics Ltd., Rehovot 76706, Israel
Moshe B Hoshen, Clalit Research Institute, Clalit Medical Services, Tel Aviv 69978, Israel
Nitzan Rosenfeld, Cancer Research UK, Cambridge Research Institute, Cambridge CB2 ORE, United Kingdom
Gideon Marshak, Institute of Oncology, Rabin Medical Center, Golda-Hasharon Hospital, Petach Tikva 49100, Israel
Yulia Kundel, Ronen Brenner, Institute of Oncology, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel
Gideon Marshak, Yulia Kundel, Ronen Brenner, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Sara Morgenstern, Institute of Pathology, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel
Sara Morgenstern, Marisa Halpern, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Marisa Halpern, Institute of Pathology, Rabin Medical Center, Golda-Hasharon Hospital, Petach Tikva 49100, Israel
Yaron Niv, Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel
Yaron Niv, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978 Israel
Author contributions: Brenner B, Hoshen MB and Purim O contributed equally to this work; Brenner B and Chajut A designed the research; Brenner B, Hoshen MB and Purim O analyzed the data; David MB, Ashkenazi K, Morgenstern S, Halpern M and Kushnir M performed the research; Brenner B, Purim O, Kundel Y, Mahrshak G and Brenner R collected the data; Brenner B, Hoshen MB, Purim O, Rosenfeld N, Niv Y and Kushnir M wrote the paper.
Correspondence to: Baruch Brenner, MD, Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel. brennerb@clalit.org.il
Telephone: +972-3-9378005  Fax: +972-3-9378045
Received: February 17, 2011
Revised: April 15, 2011
Accepted: April 22, 2011
Published online: September 21, 2011
Abstract

AIM: To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.

METHODS: The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%).

RESULTS: Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups.

CONCLUSION: This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact.

Keywords: MicroRNA; Prognosis; Recurrence; Gastric cancer