Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.
Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.
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DOI：
10.1373/clinchem.2018.290569
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发表时间：
2018-10
影响因子：
9.3
通讯作者：
Wong DTW
中科院分区：
文献类型：
--
作者：
Li F;Yoshizawa JM;Kim KM;Kanjanapangka J;Grogan TR;Wang X;Elashoff DE;Ishikawa S;Chia D;Liao W;Akin D;Yan X;Lee MS;Choi R;Kim SM;Kang SY;Bae JM;Sohn TS;Lee JH;Choi MG;Min BH;Lee JH;Kim JJ;Kim Y;Kim S;Wong DTW
胃癌（GC）的无创早期检测需要生物标志物。我们研究了唾液细胞外RNA（exRNA）生物标志物作为GC的潜在临床评价工具。前瞻性地从294名在韩国三星医疗中心接受内窥镜评估的个体（163名GC和131名非GC患者）中收集未刺激的全唾液样本。对63例GC和31例非GC患者的唾液转录组进行了分析，并用逆转录定量实时PCR（RT-qPCR）验证了mRNA生物标志物候选物。同时，对来自10名GC和10名非GC患者的唾液样本进行了microRNA（miRNA）生物标志物分析和验证。在来自GC和非GC患者的100/100个唾液样品的独立队列中用RT-qPCR验证候选生物标志物。将经验证的单个标记物配置为最佳性能面板。我们鉴定了30种mRNA和15种miRNA候选物，其表达模式与GC的存在相关。其中，12种mRNA和6种miRNA候选物通过RT-qPCR与发现队列验证，并进一步与独立队列（n = 200）验证。配置的生物标志物组由3种mRNA（SPINK 7、PPL和SEMA 4 B）和2种miRNA（MIR 140 - 5 p和MIR 301 a）组成，其在GC组中均显著下调，并且产生0.81（95%CI，0.72-0.89）的ROC曲线下面积（AUC）。当与人口统计学因素结合时，生物标志物组的AUC达到0.87（95% CI，0.80-0.93）。我们已经发现并验证了一组唾液exRNA生物标志物，其具有用于检测GC的可靠临床性能。我们的研究证明了唾液exRNA生物标志物在GC筛查和风险评估中的潜在效用。
Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72–0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80–0.93). We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.
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影响因子：
4.6
作者：
Lee KS;Oh DK;Han MA;Lee HY;Jun JK;Choi KS;Park EC
通讯作者：
Park EC
关键评估用于分类或预测的生物标志物的准确性：研究设计标准。
影响因子：
10.3
作者：
Pepe, Margaret S.;Feng, Ziding;Janes, Holly;Bossuyt, Patrick M.;Potter, John D.
通讯作者：
Potter, John D.
影响因子：
78.5
作者：
Polk, D. Brent;Peek, Richard M., Jr.
通讯作者：
Peek, Richard M., Jr.
影响因子：
7.6
作者：
Li, Y;Zhou, X;Wong, DTW
通讯作者：
Wong, DTW
影响因子：
2.3
作者：
Nomura, Abraham M. Y.;Wilkens, Lynne R.;Kolonel, Laurence N.
通讯作者：
Kolonel, Laurence N.