Hotchi Masanori, Shimada Mitsuo, Kurita Nobuhiro, Iwata Takashi, Sato Hirohiko, Morimoto Shinya, Yoshikawa Kozo, Higashijima Jun, Miyatani Tomohiko
Department of Surgery, Ehime Prefectural Central Hospital, Matsuyama 790-0024;
Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima 770-8503, Japan.
Mol Clin Oncol. 2013 Jan;1(1):137-142. doi: 10.3892/mco.2012.9. Epub 2012 Aug 9.
Although global microRNA (miRNA) expression patterns of several embryologic, physiological and oncogenic processes have been thoroughly studied, no studies are available on the role of miRNAs in pre-operative chemoradiotherapy (CRT) in rectal cancer. This study aimed to delineate the expression pattern of miRNAs for the prediction of response to CRT in rectal cancer. Rectal cancer patients (n=43), who underwent pre-operative CRT (40 Gy radiotherapy combined with S-1), were studied. RNA harvested from rectal cancer biopsy specimens prior to pre-operative CRT was hybridized to miRNA microarrays (821 genes). The response to CRT was evaluated by histopathological examination of surgically resected specimens, Response Evaluation Criteria in Solid Tumors (RECIST) and downstaging. The data of miRNA microarray were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). Two miRNAs (miR-142-3p, 223) with an increased expression that correctly differentiated responders from non-responders to CRT were identified by histopathological examination. One gene (miR-223) showed a higher, while 8 genes (miR-20b, miR-92a, let-7a*, miR-20a, miR-17*, miR-106a, miR-17 and miR-20a*) a lower expression in responders compared to nonresponders, with regard to RECIST. The 3 genes (miR-223, miR-630 and miR-126*) had a higher expression in responders compared to non-responders, with regard to downstaging. The real-time RT-PCR evaluation analysis detected a higher miR-223 level in responders compared to non-responders. Consequently, candidate miR-223 may be a new biomarker for the prediction of response to CRT and may be useful when establishing tailor-made therapies for rectal cancer.
尽管已经对几种胚胎学、生理学和致癌过程的全球微小RNA（miRNA）表达模式进行了深入研究，但关于miRNA在直肠癌术前放化疗（CRT）中的作用尚无相关研究。本研究旨在描绘miRNA的表达模式，以预测直肠癌对CRT的反应。对接受术前CRT（40 Gy放疗联合S-1）的43例直肠癌患者进行了研究。在术前CRT之前从直肠癌活检标本中提取的RNA与miRNA微阵列（821个基因）进行杂交。通过对手术切除标本的组织病理学检查、实体瘤疗效评价标准（RECIST）和降期来评估对CRT的反应。通过实时逆转录聚合酶链反应（RT-PCR）评估miRNA微阵列的数据。通过组织病理学检查鉴定出两种表达增加的miRNA（miR-142-3p、223），它们能正确区分CRT的反应者和无反应者。就RECIST而言，一个基因（miR-223）在反应者中表达较高，而8个基因（miR-20b、miR-92a、let-7a*、miR-20a、miR-17*、miR-106a、miR-17和miR-20a*）在反应者中的表达低于无反应者。就降期而言，3个基因（miR-223、miR-630和miR-126*）在反应者中的表达高于无反应者。实时RT-PCR评估分析检测到反应者中的miR-223水平高于无反应者。因此，候选miR-223可能是预测CRT反应的一种新生物标志物，在为直肠癌制定个性化治疗方案时可能有用。
