Retrospective Study
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World J Gastroenterol. Sep 14, 2014; 20(34): 12241-12248
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12241
Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer
Peng Zhang, Deng-Bo Ji, Hai-Bo Han, Yun-Fei Shi, Chang-Zheng Du, Jin Gu
Peng Zhang, Deng-Bo Ji, Chang-Zheng Du, Jin Gu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Colorectal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
Hai-Bo Han, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China
Yun-Fei Shi, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
Author contributions: Zhang P and Gu J designed the research; Zhang P, Ji DB, Han HB, Shi YF and Du CZ performed the research; Zhang P analyzed the data and wrote the paper; Gu J made critical revisions of the manuscript.
Supported by National Natural Science Foundation of China, No. 30872467, No. 81030040, No. 81201965 and No. 81372593; Beijing Natural Science Foundation, No. 7132052; and the National High Technology Research and Development Program of China (863 Program), No. 2012AA02A506
Correspondence to: Jin Gu, MD, FACS, Professor, Chairman, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Colorectal Surgery, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China. zlgujin@126.com
Telephone: +86-10-88141032 Fax: +86-10-88141032
Received: March 14, 2014
Revised: May 8, 2014
Accepted: May 29, 2014
Published online: September 14, 2014
Abstract

AIM: To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer (CRC) patients.

METHODS: A total of 304 formalin-fixed, paraffin-embedded specimens (69 paired cancer and normal tissues, 55 primary tumors of stage III CRC and matched lymph nodes, and 56 primary tumors of stage II CRC) were included in this study. The relative expression levels of miR-193a-5p in the normal mucosa, primary cancer, and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction. We evaluated the association of its expression with colorectal cancer lymph node metastasis, clinicopathological factors, and patient survival.

RESULTS: The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa (P = 0.0060). The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases (P = 0.0006), and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage (P = 0.0007). Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival (DFS) (P = 0.0026) and poor overall survival (OS) (P = 0.0003). Interestingly, for the group of patients with lymph node metastases, miR-193a-5p expression was also related to survival. Patients with low miR-193a-5p expression had decreased DFS (P = 0.0262) and poor OS (P = 0.0230). Moreover, multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS.

CONCLUSION: Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC. miR-193a-5p may be a useful biomarker for CRC diagnosis, metastasis and prognosis prediction.

Keywords: miR-193a-5p, Colorectal cancer, Lymph node metastasis, Prognosis, Biomarker

Core tip: We determined the expression of miR-193a-5p in colorectal cancer (CRC) tissues and metastatic lesions in the lymph nodes using quantitative real-time reverse transcriptase polymerase chain reaction. Downregulation of miR-193a-5p correlated with tumor progression, lymph node metastasis and poor survival in CRC patients. These findings suggest that miR-193a-5p could be used as a molecular biomarker of diagnosis, early-stage metastasis prediction, and prognosis forecast for CRC. This is believed to be the first study to investigate the relationship between miR-193a-5p expression and lymph node metastasis in CRC.