Research Papers:

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

Nobuyoshi Yamazaki, Yoshikatsu Koga _, Hirokazu Taniguchi, Motohiro Kojima, Yukihide Kanemitsu, Norio Saito and Yasuhiro Matsumura

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Oncotarget. 2017; 8:6970-6983. https://doi.org/10.18632/oncotarget.14344

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Nobuyoshi Yamazaki1,2, Yoshikatsu Koga1, Hirokazu Taniguchi3, Motohiro Kojima4, Yukihide Kanemitsu5, Norio Saito2, Yasuhiro Matsumura1

1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan

2Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan

3Pathology Division, National Cancer Center Hospital, Tokyo, Japan

4Pathology Division, National Cancer Center Hospital East, Kashiwa, Japan

5Colorectal 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


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.

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