A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

作者：Scarpati Giuseppina Della Vittoria; Falcetta Francesca; Carlomagno Chiara^*; Ubezio Paolo; Marchini Sergio; De Stefano Alfonso; Singh Vijay Kumar; D' Incalci Maurizio; De Placido Sabino; Pepe Stefano

来源：International Journal of Radiation Oncology, Biology, Physics, 2012, 83(4): 1113-1119.

DOI：10.1016/j.ijrobp.2011.09.030

• miRNA
• Predictive factors
• Preoperative chemoradiotherapy
• Rectal cancer

Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific %26quot;signature%26quot; correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. %26lt;br%26gt;Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG %26gt;1 (no pCR), was assessed by methods specifically designed for this study. %26lt;br%26gt;Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. %26lt;br%26gt;Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

• 出版日期2012-7-15