Original Article
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World J Gastroenterol. Nov 7, 2013; 19(41): 7078-7088
Published online Nov 7, 2013. doi: 10.3748/wjg.v19.i41.7078
Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype
Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho
Jae Yun Lim, So-Young Seol, Jae Yong Cho, Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea
Sun Och Yoon, Soon Won Hong, Department of Pathology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine 135-720, Seoul, South Korea
Jong Won Kim, Seung Ho Choi, Department of Surgery, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea
Jae Yun Lim, Ju-Seog Lee, Department of Systems Biology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Author contributions: Cho JY and Lee JS designed the study; Lim JY, Yoon SO, Seol SY, Hong SW, Kim JW and Choi SH contributed to performing experiment and acquisition of data; Lim JY and Cho JY analyzed and interpreted the data; Lim JY and Cho JY wrote the paper.
Supported by The Faculty Research Grant of Yonsei University College of Medicine (6-2011-0113); the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, No. 2010-0024248
Correspondence to: Jae Yong Cho, MD, PhD, Professor, Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, South Korea. chojy@yuhs.ac
Telephone: +82-2-20194363 Fax: +82-2-34633882
Received: March 26, 2013
Revised: July 2, 2013
Accepted: July 9, 2013
Published online: November 7, 2013
Processing time: 235 Days and 0.4 Hours
Abstract

AIM: To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein expression.

METHODS: Array technologies were used to generate 1146 microRNAs and 124 proteins expression profiles of samples from 60 patients with gastric cancer. For the integrative analysis, we used established mRNA expression data published in our previous study. Whole mRNA expression levels were acquired from microarray data for 60 identical gastric cancer patients. Two gastric adenocarcinoma subgroups with distinct mRNA expression profiles presented distinctly different prognoses. MicroRNA and protein expression patterns were compared between gastric cancer tissue and normal gastric tissue and between two different prognostic groups. Aberrantly expressed microRNA, associated mRNA, and protein in patients with poor-prognosis gastric cancer were validated by quantitative reverse transcription polymerase chain reaction and immunochemistry in independent patients.

RESULTS: We obtained the expression data of 1146 microRNAs and 124 cancer-related proteins. Four microRNAs were aberrantly expressed in the two prognostic groups and in cancer vs non-cancer tissues (P < 0.05). In the poor-prognosis group, miR-196b, miR-135b, and miR-93 were up-regulated and miR-29c* was down-regulated. miR-196b expression positively correlated with Homeobox A10 (HOXA10) expression (r = 0.726, P < 0.001), which was significantly increased in poor-prognosis patients (P < 0.001). Comparing gastric cancer with non-cancer tissues, 46/124 proteins showed differential expression (P < 0.05); COX2 (P < 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group.

CONCLUSION: Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. Elucidation of the biologic function of miR-196b and HOXA10 is warranted.

Keywords: Gastric cancer; Gene expression; Microarray; MicroRNA; miR-196b; Homeobox A10

Core tip: Using an integrative analysis of the tumor transcriptome and protein expression profiles obtained by microarray techniques, we have elucidated the molecular biologic characteristics of a poor prognosis gastric cancer subgroup. Overexpression of miR196b and Homeobox A10 are implicated in gastric cancer, particularly in tumors with poor prognosis features. We anticipate this integrative approach will contribute to the characterization of cancer heterogeneity and the development of personalized therapy through the identification of cancer targets.