Circulating Plasma miRNAs as Potential Biomarkers of Non-Small Cell Lung Cancer Obtained by High-Throughput Real-Time PCR Profiling
Circulating Plasma miRNAs as Potential Biomarkers of Non-Small Cell Lung Cancer Obtained by High-Throughput Real-Time PCR Profiling
复制标题
通过高通量实时 PCR 分析获得循环血浆 miRNA 作为非小细胞肺癌的潜在生物标志物
DOI：
10.1158/1055-9965.epi-18-0723
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发表时间：
2019-02-01
影响因子：
3.8
通讯作者：
Gou, Deming
中科院分区：
文献类型：
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作者：
Niu, Yanqin;Su, Mingyang;Gou, Deming
背景：由于稳定性和敏感性有限，作为非侵袭性生物标志物的循环miRNAs迄今尚未在临床上用于非小细胞肺癌的早期诊断和预后判断。因此，寻找更可靠的生物标志物(S)势在必行。方法：采用最灵敏的定量逆转录聚合酶链式反应方法S-Poly(T)Plus，从全基因组miRNA图谱中筛选差异表达的miRNA。通过三阶段筛选和两个验证过程对437例NSCLC和415例对照的miRNA候选进行了验证。结果：腺癌(ADC)和鳞癌(SCC)标本中有7个和9个miRNA与对照组有显著差异，其中NSCLC有5个通用的生物标志物(ADC或SCC)。11个miRNAs中有10个可以区分非小细胞肺癌早期(I期)和健康人。风险评分从验证集-1获得，并使用ROC曲线下面积高的ROC曲线进行检验，ADC和SCC的ROC曲线下面积分别为0.89和0.96。最终，验证集-2对ADC的敏感性为94%，特异性为91.6%，对鳞癌的敏感性为98.5%，特异性为51.5%。结论：综合考虑，7种miRNAs和9种miRNAs可分别为ADC和SCC的诊断和预后提供无创性的生物标志物。
Background: Because of limited stability and sensitivity, circulating miRNAs as noninvasive biomarkers have not so far been used for early diagnosis and prognosis of non-small cell lung cancer (NSCLC) in clinic. Therefore, it is imperative to find more reliable biomarker(s).Methods: We performed one of most sensitive qRT-PCR assays, S-Poly(T) Plus, to select differently expressed miRNAs from genome-wide miRNA profiling. miRNA candidates were validated through a three-phase selection and two validation processes with 437 NSCLC cases and 415 controls.Results: A unique set of 7 and 9 miRNAs differed significantly in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) samples compared with those in controls, of which, there were 5 universal biomarkers for NSCLC (ADC or SCC). Ten of 11 miRNAs could discriminate early stage (stage I) of NSCLC from healthy individuals. Risk score was obtained from the validation set-1 and was tested using the ROC curves with a high area under ROC curve of 0.89 in ADC and 0.96 in SCC. Ultimately, potential biomarkers and the risk score were verified by the validation set-2 with a sensitivity of 94% and a specificity of 91.6% in ADC, and a sensitivity of 98.5% and a specificity of 51.5% in SCC, respectively.Conclusions: Taken together, 7 miRNAs and 9 miRNAs may provide noninvasive biomarkers for diagnosis and prognosis in ADC and SCC, respectively.Impact: On the basis of our sensitive and accurate method, we hope that these candidate miRNAs may have strong impact on the early lung cancer diagnosis.