Abstract 4917: High expression of miR-181c in tumor tissue as a recurrence marker of Dukes B colorectal cancer
Authors: Yoshikatsu Koga, Nobuyoshi Yamazaki, Hirokazu Taniguchi, Motohiro Kojima, Yukihide Kanemitsu, Norio Saito, Yasuhiro Matsumura
Journal: Cancer Research (2016)

Abstract Background &amp; Aims: A standard treatment for Dukes B colorectal cancer (CRC) which invades deeply through the muscularis propria without lymph node metastasis and distant metastasis is surgical resection without any additional chemotherapy. However, tumor recurrence is occurred in approximately 20% of these patients after curative resection. To date, there were no biomarkers for detecting the high risk group for tumor recurrence of Dukes B CRC. In the present study, miRNAs extracted from both frozen tissues and formalin-fixed paraffin-embedded (FFPE) tissues of CRC were investigated for a candidate for detecting the high risk group in Dukes B CRC. Methods: Patients with histologically confirmed as Dukes B CRC were enrolled; 10 patients (5 patients with recurrence and 5 patients without recurrence) for preliminary study, 80 patients for training cohort, and 57 patients for validation cohort. First, comprehensive analysis of miRNAs was performed to select candidate miRNAs associated with recurrence using a high-sensitivity miRNA array chip in the preliminary study. Next, the candidate miRNAs were analyzed by real-time RT-PCR using miRNA extracted from frozen tissue and FFPE tissue in the training cohort. Finally, miR-181c was assessed by real-time RT-PCR using miRNA extracted from FFPE tissue in the validation cohort. Results: In the preliminary study, 15 miRNAs were expressed significantly higher in the cancer tissue with recurrence than that without recurrence (P &amp;lt; 0.05) and selected as candidates for further study. Regarding let-7a, -7d, -7e, miR-23c, -26b, -128a, -151-5p, and -181c, tumor recurrence in the high expression group of these miRNAs was observed significantly higher than that in the low expression group in the training cohort using frozen tissue (P &amp;lt; 0.05). According to multivariate analysis including pathological factors, the high expression of miR-181c was detected as an independent predictive factor for recurrence (P = 0.001, OR: 9.43, 95%CI: 2.57-34.48). The same result was observed in the training cohort using FFPE tissue (P = 0.003, OR: 7.46, 95%CI: 1.97-28.57). In the validation cohort using the FFPE tissue, the recurrence rates of Dukes B CRC patients with high miR-181c expression and low miR-181c expression were 4.5% and 38.5%, respectively (P &amp;lt; 0.001). Conclusions: miR-181c expression in CRC tissue (both frozen and FFPE) may be a useful predictive biomarker for tumor recurrence of Dukes B CRC. Citation Format: Yoshikatsu Koga, Nobuyoshi Yamazaki, Hirokazu Taniguchi, Motohiro Kojima, Yukihide Kanemitsu, Norio Saito, Yasuhiro Matsumura. High expression of miR-181c in tumor tissue as a recurrence marker of Dukes B colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4917.