Exosomal microRNA-199b-5p as a potential circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer.

Abstract

e15161 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision has become the standard treatment for locally advanced rectal cancer (LARC). However, the effect of CRT varies from complete response to complete resistance, and predicting response to CRT have not been well characterized yet. Previous studies have shown the potential of micro-RNA (miRNA) based approaches to enhance tumor radiation response. Accordingly, the present study attempted to identify biomarkers to predict response for preoperative CRT using comprehensive miRNA analysis in patients with LARC. Methods: This study included 65 rectal cancer tissues and 90 serum samples from patients who diagnosed with LACR and received preoperative CRT at Kyungpook National University Chilgok Hospital. Tissue specimens and serum samples were collected before CRT to evaluate the biologic differences between the good CRT response group and the poor CRT response group. For discovery of specific miRNAs, 800 miRNAs were analyzed using NanoString in 30 rectal cancer tissues. Thereafter, a total of 65 tissues, and 90 serum samples were investigated using real-time PCR for validation. Results: The median age was 59 years (range, 30-82), and the ratio of male to female was 3.05 to 1. The pathologic stages after preoperative CRT were as follows: pathologic complete response (n=13, 14.4%), pathologic stage I (n=13, 14.4%), pathologic stage II (n=27, 30.0%), pathologic stage III (n=28, 31.1%), and pathologic stage IV (n=9, 10.0%). In the discovery set, 16 target miRNAs were detected. In the validation set with tissue specimens, expression of 3 miRNAs (miR-199a/b-3p ( p=0.032), miR-199a-5p ( p=0.023), miR-199b-5p ( p=0.005)) was significantly upregulated which was associated with better response of CRT. Moreover, among the 3 candidate miRNAs, miR-199b-5p level was significantly upregulated in serum, and it was also found to be related with better response of CRT in LARC (pathologic stage 0/I versus II/III/IV, p=0.027). Conclusions: In the present study, high level of exosomal miR-199b-5p was associated with better response, suggesting it to be a promising non-invasive biomarker to predict response of CRT in patients with LARC. Accordingly, specific miRNAs can be predictive biomarker or therapeutic target to overcome radiotherapy resistance in LARC with a functional study.