Up-regulated Circulating miR-106a by DNA Methylation Promised a Potential Diagnostic and Prognostic Marker for Gastric Cancer.
Up-regulated Circulating miR-106a by DNA Methylation Promised a Potential Diagnostic and Prognostic Marker for Gastric Cancer.
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DOI：
10.2174/1871520615666150716110657
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发表时间：
2016-08
影响因子：
2.8
通讯作者：
Renshun Yuan;G. Wang;Zhihua Xu;Hong Zhao;Huabin Chen;Ye Han;Bin Wang;Jin Zhou;Hao Hu;Zhaoji Guo;Hugang Shen;Xiaofeng Xue
中科院分区：
文献类型：
--
作者：
Renshun Yuan;G. Wang;Zhihua Xu;Hong Zhao;Huabin Chen;Ye Han;Bin Wang;Jin Zhou;Hao Hu;Zhaoji Guo;Hugang Shen;Xiaofeng Xue
以往的研究表明，miRNA表达异常是恶性肿瘤的一个显着特征。我们的目的是探索 miR-106a 作为胃癌（GC）潜在诊断和预后生物标志物的作用。首先采用qPCR检测28对GC癌组织及癌旁组织、48对GC患者术前、术后血浆样本以及22份健康对照血浆样本中miR-106a的表达水平。结果显示，肿瘤组织中miR-106a的水平（2.700±2.565）显着高于癌旁组织（1.321±0.904）（p<0.05）。此外，与健康对照者（2.594±2.329）相比，GC患者血浆中miR-106a的表达水平（9.479±5.595）显着上调（p<0.05），而胃切除术后GC患者血浆中miR-106a的表达量显着下降。进一步统计数据显示，miR-106a高表达与GC的淋巴转移程度、TNM分期密切相关。我们还应用 ROC 曲线来评估 miR-106a 作为 GC 患者的诊断标志物。结果，组织样本的敏感性和特异性分别为60.4%、68.2%，血浆样本的敏感性和特异性分别为72.9%、63.6%。最后，我们通过甲基化特异性PCR（MSP）检测了28对GC组织中miR-106a启动子的甲基化状态，结果显示癌组织中的甲基化率为53.6%，癌旁组织中的甲基化率为85.7%。此外，结果表明miR-106a的启动子低甲基化与其高表达有关。我们的研究表明，miR-106a 可能作为进行性 GC 的潜在预后指标，并且通过启动子低甲基化上调循环 miR-106a，可能被提议作为 GC 的候选诊断和预后指标。
Previous studies suggested that abnormal miRNA expression was a significant characteristic of malignant tumors. We aimed to explore the role of miR-106a as the potential diagnostic and prognostic biomarker in gastric cancer (GC). Firstly, the expression level of miR-106a was detected by qPCR in 28 pairs of GC cancer tissues and adjacent tissues, 48 pairs of plasma samples before and after operation from GC patients, and 22 plasma samples from healthy controls. It had revealed that the level of miR-106a in tumor tissues (2.700±2.565) was significantly higher compared to adjacent tissues (1.321±0.904) (p<0.05). Besides, the expression level of miR-106a in plasma of GC (9.479±5.595) was significantly up-regulated compared with healthy controls (2.594±2.329) (p<0.05), while a remarkable decline of miR- 106a expression was observed in plasma of GC patients after gastrectomy. Further statistic data showed high miR-106a expression was closely related to the degree of lymphatic metastasis and TNM staging of GC. We also applied ROC curve in order to evaluate miR-106a as a diagnostic marker for GC patients. As a result, the sensitivity and specificity were 60.4%, 68.2% in tissue samples and 72.9%, 63.6% in plasma samples, respectively. At last, we explored the methylation status of miR-106a promoter in 28 paired GC tissues through methylation-specific PCR (MSP), the result showed that the methylation rate was 53.6% in cancer tissues and 85.7% in adjacent tissues. Moreover, the result indicated that promoter hypomethylation of miR- 106a is related to its high expression. Our research indicated that miR-106a might serve as a potential prognostic indicator in progressive GC and up-regulated circulating miR-106a by promoter hypomethylation, might be proposed as a candidate diagnostic and prognostic indicator for GC.