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

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• 作者：Giuseppina Della Vittoria Scarpati ; M.D. ; Ph.D.^&lowast ; ; ¹ ; Francesca Falcetta ; Ph.D.^&dagger ; ; ¹ ; Chiara Carlomagno ; M.D. ; Ph.D.^&lowast ; ; ^{chiara.carlomagno@unina.it} ; Paolo Ubezio ; Ph.D.^&dagger ; ; Sergio Marchini ; Ph.D.^&dagger ; ; Alfonso De Stefano ; M.D.^&lowast ; ; Vijay Kumar Singh ; Ph.D.^&Dagger ; ; Maurizio D’ ; Incalci ; M.D.^&dagger ; ; Sabino De Placido ; M.D.^&lowast ; ; Stefano Pepe ; M.D. ; Ph.D.^§ ;
• 关键词：miRNA ; Predictive factors ; Preoperative chemoradiotherapy ; Rectal cancer
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2012
• 期刊代码：136_03603016
• 类别：med
• 出版时间：15 July, 2012
• 卷：83
• 期：4
• 页码：1113-1119
• 文件大小：783 K

摘要

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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 鈥渟ignature鈥?correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy.

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 >1 (no pCR), was assessed by methods specifically designed for this study.

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鈭? 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.

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.