Retrospective Study
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World J Gastroenterol. Aug 28, 2014; 20(32): 11340-11346
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11340
Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients
Li-Li Wang, Lu-Tao Du, Juan Li, Yi-Min Liu, Ai-Lin Qu, Yong-Mei Yang, Xin Zhang, Gui-Xi Zheng, Chuan-Xin Wang
Li-Li Wang, Lu-Tao Du, Juan Li, Yi-Min Liu, Ai-Lin Qu, Yong-Mei Yang, Xin Zhang, Gui-Xi Zheng, Chuan-Xin Wang, Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Qu AL and Yang YM performed the research and data analysis; Li J and Liu YM summarized the RT-qPCR results; Zhang X and Zheng GX assisted in patient recruitment and patient interviews; Wang LL, Du LT and Wang CX designed the study and wrote the manuscript.
Supported by Grants from the National Key Clinical Medical Specialties Foundation and the National Natural Science Foundation of China, No. 81271916 and No. 81301506
Correspondence to: Chuan-Xin Wang, MD, PhD, Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. cxwang@sdu.edu.cn
Telephone: +86-531-82166801 Fax: +86-531-86927544
Received: December 11, 2013
Revised: February 24, 2014
Accepted: May 23, 2014
Published online: August 28, 2014
Abstract

AIM: To investigate microRNA-133a (miR-133a) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis.

METHODS: Quantitative real-time polymerase chain reaction was used to measure levels of miR-133a in tumor samples and adjacent non-cancerous tissues from 169 patients undergoing radical resection for CRC. The associations between miR-133a expression and patient age, sex, as well as clinicopathologic parameters, such as tumor size, differentiation, location, invasion depth, metastasis, tumor-node-metastasis (TNM) stage and overall patient survival, were analyzed by Mann-Whitney U and Kruskal-Wallis tests. The Kaplan-Meier method and Cox proportional hazards regression analyses were performed to estimate the prognostic factors for patient survival prediction.

RESULTS: The expression of miR-133a was significantly downregulated in CRC tissues compared with adjacent non-cancerous tissues (P < 0.05). This reduction was associated with the depth of the local invasion, poor differentiation, lymph node metastasis and advanced disease (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-133a expression had poorer overall survival (OS) than those with high miR-133a expression (P < 0.001). Univariate analysis revealed statistically significant correlations between OS and miR-133a level, tumor local invasion, lymph node metastasis and TNM stage (P < 0.001). Furthermore, miR-133a levels and TNM stage were independently associated with OS (HR = 0.590, 95%CI: 0.350-0.995, P < 0.05; and HR = 6.111, 95%CI: 1.029-36.278, P < 0.05, respectively).

CONCLUSION: The downregulation of miR-133a may play an important role in the progression of CRC and can be used as an independent factor to determine CRC prognosis.

Keywords: Colorectal cancer, Biomarker, MicroRNA-133a, Prognosis, Real-time polymerase chain reaction

Core tip: In the present study, the level of microRNA-133a (miR-133a) was found to be downregulated in colorectal cancer (CRC) tissues. The altered expression of miR-133a was significantly associated with malignant behavior, including tumor cell differentiation, local invasion, lymph node metastasis and tumor-node-metastasis stage. Multivariate analysis suggested that low expression of miR-133a is an independent prognostic factor for CRC. Furthermore, the data suggest that miR-133a may play a critical role in CRC progression, and thus may serve as a potential therapeutic target.