Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer
Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer
复制标题
血浆 miR-122 和 miR-192 作为早期检测胃癌远处转移的潜在新型生物标志物。
DOI：
10.3892/or.2014.3004
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发表时间：
2014-04-01
期刊：
影响因子：
4.2
通讯作者：
Bi, Feng
中科院分区：
文献类型：
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作者：
Chen, Qingjuan;Ge, Xiaojun;Bi, Feng
本研究的目的是确定血浆中特异性microRNA（miRNAs）水平是否与胃癌（GC）远处转移（DM）相关。对12对有远处转移的胃癌（GC/DM）和无远处转移的胃癌（GC/NDM）的样本进行miRNA谱分析;鉴定出14个差异表达的miRNA用于进一步检查。使用定量逆转录PCR（qRT-PCR）在独立验证集上验证这14种miRNA，鉴定出2种差异表达的miRNA（miR-122和miR-192）。在疾病对照组、自身配对的血浆组以及最后在体外胃细胞系中对这两种候选miRNA进行进一步验证。结果显示，与GC/NDM和健康对照（HC）相比，GC/DM样本中血浆miR-122水平显着降低，血浆miR-192水平显着升高（均P<0.01）。GC/DM患者血浆miR-122水平再次低于良性胃溃疡（BGC）和慢性胃炎（CG）患者（P <0.01），而血浆miR-192水平再次高于良性胃溃疡（BGC）和慢性胃炎（CG）患者（P<0.01）。与远处转移前相比，远处转移后患者miR-122水平显著降低，而miR-192水平显著升高（P<0.01）。在CTC 105和CTC 141细胞中，与GES-1细胞中的水平相比，miR-122水平中度降低，miR-192水平显著升高。ROC分析显示血浆miR-122的AUC为0.808（95%CI，0.712-0.905; P<0.01），血浆miR-192的AUC为0.732（95%CI，0.623-0.841; P<0.01），用于区分GC/DM和GC/NDM。血浆中miR-122的高表达独立地有助于更有利的GC预后（风险比，0.262; 95%CI，0.164-0.816; P=0.038;考克斯回归分析），而miR-192水平与总生存时间无关。我们的研究结果表明，评估循环miR-122水平降低和循环miR-192水平升高有可能改善GC中DM的早期检测。胃癌中较高的血浆miR-122水平可能表明预后良好。
The aim of the present study was to ascertain whether plasma levels of specific microRNAs (miRNAs) are associated with distant metastasis (DM) in gastric cancer (GC). miRNA profiling was performed on 12 pairs of samples of gastric cancer with distant metastasis (GC/DM) and gastric cancer with no distant metastasis (GC/NDM); 14 differentially expressed miRNAs were identified for further inspection. Validation of these 14 miRNAs using quantitative reverse transcription PCR (qRT-PCR) on an independent validation set identified 2 differentially expressed miRNAs (miR-122 and miR-192). further validation of these two candidate miRNAs was conducted in a disease control set, a self-paired plasma set and finally in gastric cell lines in vitro. The results revealed that when compared with GC/NDM and healthy controls (HCs), plasma levels of miR-122 were significantly lower and plasma levels of miR-192 were significantly higher in GC/DM samples (both P<0.01). The plasma miR-122 level was again lower and the plasma miR-192-level was again higher in patients with GC/DM than in patients with benign gastric ulcer (BGC) and chronic gastritis (CG) (P<0.01). Compared to the level in patients with pre-distant metastases, miR-122 was significantly decreased while miR-192 was markedly elevated in patients with post-distant metastases (P<0.01). In CTC105 and CTC141 cells, miR-122 levels were moderately lower and miR-192 levels were markedly higher when compared to the levels in the GES-1 cells. ROC analyses showed that the AUC for plasma miR-122 was 0.808 (95% CI, 0.712-0.905; P<0.01), and the AUC for plasma miR-192 was 0.732 (95% CI, 0.623-0.841; P<0.01) for distinguishing GC/DM from GC/NDM. High expression of miR-122 in plasma independently contributed to a more favorable prognosis for GC (hazard ratio, 0.262; 95% CI, 0.164-0.816; P=0.038; Cox regression analysis), whereas the miR-192 level was not associated with the overall survival time. Our results demonstrated that assessment of decreased circulating miR-122 and elevated circulating miR-192 levels has the potential to improve early detection of DM in GC. Higher plasma levels of miR-122 in GC may indicate a favorable prognosis.