MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.
MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.
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DOI：
10.1186/1748-717x-7-195
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发表时间：
2012-11-20
期刊：
影响因子：
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通讯作者：
Slaby O
中科院分区：
文献类型：
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作者：
Svoboda M;Sana J;Fabian P;Kocakova I;Gombosova J;Nekvindova J;Radova L;Vyzula R;Slaby O
直肠癌约占所有结直肠癌（CRC）的三分之一，属于全球癌症死亡的主要原因之一。局部晚期直肠癌（cT 3/4和/或cN+）的标准治疗包括使用氟尿嘧啶（卡培他滨或5-氟尿嘧啶）进行新辅助放化疗，然后进行根治性手术切除。不幸的是，相当大比例的肿瘤对新辅助治疗没有足够的反应，这些患者有复发的风险。微小RNA（microRNAs，miRNAs）是一类小分子非编码RNA，在包括直肠癌在内的多种癌症的发病机制中起重要作用。miRNAs可能为直肠癌患者提供新的预测生物标志物。我们选择了20例接受新辅助放化疗的晚期直肠癌患者，其肿瘤被归类为对治疗最敏感或耐药。使用大规模miRNA表达谱比较这两组。8种miRNAs的表达水平在两组之间存在显著差异。miR-215、miR-190 b和miR-29 b-2* 在无应答者中过表达，let-7 e、miR-196 b、miR-450 a、miR-450 b-5 p和miR-99 a * 在应答者中显示出更高的表达水平。使用这些miRNA，10个应答者中的9个和10个无应答者中的9个（p < 0.05）已被正确分类。我们的初步研究表明，miRNA是参与直肠癌对放化疗反应的机制的一部分，miRNA可能是此类患者有希望的预测生物标志物。在我们鉴定的大多数miRNA（miR-215、miR-99 a *、miR-196 b、miR-450 b-5 p和let-7 e）中，它们的表达与对胸苷酸合成酶抑制剂的辐射抗性或化学抗性之间的联系已经建立。
Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.