MicroRNA-21 predicts response to preoperative chemoradiotherapy in locally advanced rectal cancer

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Abstract
The treatment of choice for locally advanced rectal cancer is preoperative chemoradiotherapy. Despite half of patients do not respond and suffer unnecessary toxicities and surgery delays, there are no biomarkers to guide preoperative CRT outcome. MicroRNA-21 has been related to acquisition of 5-fluorouracil resistance; however, its potential predictive value of response to preoperative chemoradiotherapy in locally advanced rectal cancer remains unknown. Nighty-two patients diagnosed with locally advanced rectal cancer who were preoperatively treated with chemoradiotherapy were selected for this study. Moreover, microRNA-21 expression was quantified in formalin-fixed paraffin-embedded biopsies from this cohort, and the results obtained were correlated with clinical and molecular characteristics, pathological response, and outcome. MicroRNA-21 was found overexpressed in 77.6 % cases, and significantly correlated with tumor grade after preoperative chemoradiotherapy (P = 0.013) and with pathological response (P = 0.013). The odds ratio of having miR-21 overexpression and not getting a respond to chemoradiotherapy resulted in 9.75 CI 2.24 to 42. Sensitivity, specificity, negative predictive values, and positive predictive value were 86.6, 60, 42.8, and 92 %, respectively. Multivariate analysis confirmed the clinical significance of miR-21 determining preoperative chemoradiotherapy response. MicroRNA-21 expression efficiently predicts preoperative chemoradiotherapy pathological response in locally advanced rectal cancer.

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