Abstract 1491: Tissue miRNA as a predictive marker for recurrence of Dukes B colorectal cancer

Abstract

Abstract Background:Colorectal cancer (CRC) diagnosed at an early stage is curable, thus, a standard treatment for Dukes B CRC which invades deeply through the muscularis propria without lymph node metastasis and distant metastasis is surgically resectable without any additional chemotherapies. However, the recurrence rate of Dukes B after curative resection is approximately 20%. Although clinical and pathological factors have been investigated in order to characterize the high risk of the recurrence in Dukes B CRC, there were no robust biomarkers suitable for detecting the high risk group. Several microRNAs (miRNAs) have appeared to be associated with CRC and some are under evaluation for a biomarker to detect CRC in serum or fecal samples. In this study, miRNAs isolated from CRC tissue were investigated for a proper biomarker for extracting the high risk group in Dukes B CRC. Methods: Patients with histologically confirmed Dukes B CRC were enrolled in this study. Tissue miRNAs extracted from the cancer tissue and normal adjacent tissue of 5 patients with recurrence were compared with those from 5 patients without recurrence, using a high-sensitivity miRNA chip, in order to select the candidate miRNAs. The candidate miRNAs associated with recurrence were then analyzed by real-time RT PCR using tissue miRNA of 14 patients with recurrence and 66 patients without recurrence. The corresponding relapse-free survival (RFS) was analyzed using the Kaplan-Meier method. Results: From the comprehensive analysis, using a high-sensitivity miRNA chip, the following 14 miRNAs were selected as candidates for further study; let-7a, -7d, -7e, miR-18b, -23c, -128a, -146b-5p, -148b, -151-5p, -181c, -221, -222, -361-5p, and -500a*. The expressions of let-7d, miR-18b, -23c, -148b, -151-5p, -181c, and -361-5p in the recurrent group were significantly higher than those in the recurrence-free group, using univariate analysis (P < 0.05). These seven miRNAs and two histopathological factors, namely pathological type and tdepth of umor invasion, were studied using multivariate analysis. Three miRNAs, miR-23c (P = 0.04, odds ratio [OR]: 21.0, 95% confidence interval [CI]: 2.65-167.4), miR-151-5p (P = 0.01, OR: 7.8, 95% CI: 1.57-38.4), and miR-181c (P = 0.006, OR: 10.0, 95% CI: 1.94-51.9), were detected as independent predictive factors of recurrence. All patients with low expression of these 3 miRNAs (N = 25) survived over 60 months without recurrence. Meanwhile, recurrent tumor occurred within 36 months in all patients with high expression of these 3 miRNAs (N = 3). Conclusion: The miRNAs selected in the present study may be a operationally useful predictors of CRC recurrence. Furthermore, there is a possibility to improve prediction performance by combining several miRNA levels. Citation Format: Nobuyoshi Yamazaki, Yoshikatsu Koga, Norio Saito, Yasuhiro Matsumura. Tissue miRNA as a predictive marker for recurrence of Dukes B colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1491. doi:10.1158/1538-7445.AM2014-1491