Genome-Wide lncRNA Microarray Profiling Identifies Novel Circulating lncRNAs for Detection of Gastric Cancer.

Genome-Wide lncRNA Microarray Profiling Identifies Novel Circulating lncRNAs for Detection of Gastric Cancer.
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全基因组 lncRNA 微阵列分析鉴定出用于检测胃癌的新型循环 lncRNA

DOI:
10.7150/thno.16044
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发表时间:
2017
期刊:
影响因子:
12.4
通讯作者:
Chen L
Chen L
中科院分区:
医学1区
文献类型:
--
作者:
Zhang K;Shi H;Xi H;Wu X;Cui J;Gao Y;Liang W;Hu C;Liu Y;Li J;Wang N;Wei B;Chen L

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长链非编码RNA(lncRNA)可以作为基于血液的癌症检测生物标志物。为了鉴定胃癌(GC)的新lncRNA生物标志物,我们首次在两组样本中进行了全基因组lncRNA筛选分析:来自GC患者的五对术前和术后第14天血浆样本,以及来自肿瘤和邻近正常组织的组织样本。然后在三个独立的阶段对候选肿瘤相关lncRNA进行定量和评估,包括321名参与者。还在GC细胞系和相应的培养基中测量lncRNA的表达水平。使用逻辑回归构建生物标志物组,基于lncRNA的指数I和基于癌胚抗原(CEA)的指数II,并比较其诊断性能。绘制了Fagan列线图,以便于临床应用。结果,我们鉴定了五种新的血浆lncRNA,(TINCR、CCAT 2、AOC 4P、BANCR和LINC 00857),当在基于lncRNA的指数I中组合时,其优于基于CEA的指数II(P < 0.001),并且可以区分GC患者和健康对照,受试者工作曲线下面积(AUC)为0.91(95%置信区间(CI):0.88-0.95)。术后第14天,基于lncRNA的指数显著降低(P = 0.016),表明其能够监测肿瘤动力学。lncRNA指数的高值与肿瘤大小(P = 0.036)、浸润深度(P = 0.025)、淋巴结转移(P = 0.012)和更晚期的肿瘤分期(P = 0.003)相关。基于lncRNA的指数也能够区分GC患者与癌前个体和胃肠道间质瘤患者,AUC值分别为0.82(95%CI:0.71-0.92)和0.80(95%CI:0.68-0.91)。总之,我们的研究结果表明,这五个血浆lncRNA的面板可以作为一组新的诊断生物标志物GC检测。
Long non-coding RNAs (lncRNAs) can serve as blood-based biomarkers for cancer detection. To identify novel lncRNA biomarkers for gastric cancer (GC), we conducted, for the first time, genome-wide lncRNA screening analysis in two sets of samples: five paired preoperative and postoperative day 14 plasma samples from GC patients, and tissue samples from tumor and adjacent normal tissues. Candidate tumor-related lncRNAs were then quantitated and evaluated in three independent phases comprising 321 participants. The expression levels of lncRNAs were also measured in GC cell lines and the corresponding culture medium. Biomarker panels, lncRNA-based Index I and carcinoembryonic antigen (CEA)-based Index II, were constructed using logistic regression, and their diagnostic performance compared. Fagan's nomogram was plotted to facilitate clinical application. As a result, we identified five novel plasma lncRNAs (TINCR, CCAT2, AOC4P, BANCR and LINC00857), which, when combined in the lncRNA-based Index I, outperformed the CEA-based Index II (P < 0.001) and could distinguish GC patients from healthy controls with an area under the receiver-operating curve (AUC) of 0.91 (95% confidence interval (CI): 0.88-0.95). The lncRNA-based index decreased significantly by postoperative day 14 (P = 0.016), indicating its ability to monitor tumor dynamics. High values of the lncRNA-based index were correlated with tumor size (P = 0.036), depth of invasion (P = 0.025), lymphatic metastasis (P = 0.012) and more advanced tumor stages (P = 0.003). The lncRNA-based index was also able to discriminate GC patients from precancerous individuals and patients with gastrointestinal stromal tumor with AUC values of 0.82 (95% CI: 0.71-0.92) and 0.80 (95% CI: 0.68-0.91), respectively. Taken together, our findings demonstrate that this panel of five plasma lncRNAs could serve as a set of novel diagnostic biomarkers for GC detection.
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