High expression of miR-181c as a predictive marker of recurrence in stage II colorectal cancer

// Nobuyoshi Yamazaki 1, 2 , Yoshikatsu Koga 1 , Hirokazu Taniguchi 3 , Motohiro Kojima 4 , Yukihide Kanemitsu 5 , Norio Saito 2 , Yasuhiro Matsumura 1 1 Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan 2 Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan 3 Pathology Division, National Cancer Center Hospital, Tokyo, Japan 4 Pathology Division, National Cancer Center Hospital East, Kashiwa, Japan 5 Colorectal Surgery Division, National Cancer Center Hospital, Tokyo, Japan Correspondence to: Yoshikatsu Koga, email: ykoga@east.ncc.go.jp Keywords: colorectal cancer, miR-181c, tissue microRNA, predictor of recurrence Received: February 15, 2016      Accepted: December 16, 2016      Published: December 28, 2016 ABSTRACT INTRODUCTION: A standard treatment for stage II colorectal cancer (CRC) is surgical resection without adjuvant chemotherapy. However, the recurrence rate of these patients is approximately 20%. To date, there are no robust biomarkers suitable for predicting recurrence in stage II CRC patients. In this study, microRNAs (miRNAs) extracted from CRC tissues were examined for a possible biomarker to predict recurrence in stage II CRC patients. RESULTS: From the comprehensive analysis, 15 miRNAs were selected as candidates for further study. Regarding let-7a, -7d, -7e, miR-23c, -26b, -128a, -151-5p, and -181c, recurrence rates in training cohort patients with higher expression of these miRNAs isolated from their frozen tissues samples were significantly higher than those with lower expression ( P < 0.05). According to multivariate analysis, the higher expression of miR-181c was detected as an independent predictive factor of recurrence ( P = 0.001, OR: 9.43, 95% CI: 2.57–34.48). Results were similar in miR-181c extracted from FFPE tissues obtained from the training cohort ( P = 0.003, OR: 7.46, 95% CI: 1.97–28.57). In the validation cohort using FFPE tissues, the recurrence rate in patients with higher miR-181c expression was significantly higher than those with lower miR-181c expression ( P < 0.001). MATERIAL AND METHODS: Comprehensive analysis using a highly sensitive miRNA chip was initially performed to select candidate miRNAs associated with recurrence. Candidate miRNAs were analyzed by real-time RT-PCR using RNA from frozen and formalin-fixed, paraffin-embedded (FFPE) tissues. CONCLUSIONS: Higher expression of miR-181c may be a useful recurrence predictor of stage II CRC patients.