Wei Jia, Yang Lu, Wu Yi-Ning, Xu Jian
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
J Cancer. 2020 Jan 1;11(6):1325-1333. doi: 10.7150/jca.38048. eCollection 2020.
: Pancreatic cancer (PC) is a highly malignant tumor with no effective early diagnostic biomarkers. This study was performed to screen and identify serum microRNAs (miRNAs) as noninvasive biomarkers for PC diagnosis. : Two upregulated miRNAs were selected by integrated analysis of three independent GEO datasets. Then, the expressions of two miRNAs in serum were determined by quantitative reverse-transcription PCR among 120 PC patients, 40 benign disease controls and 40 healthy controls. The correlation between serum miRNAs and clinical characteristics was analyzed. The diagnostic utility of miRNAs was compared to CA19-9 using receiver operating characteristic curve analysis. : We discovered miR-1290 and miR-1246 were upregulated in PC patients through GEO datasets analysis. Serum miR-1290 and miR-1246 expression levels were elevated in PC patients compared to all controls and dramatically decreased after tumor resection (all P<0.001). The area under the curve (AUC) for miR-1290 was larger than miR-1246 and CA19-9 (miR-1290: 0.91; miR-1246: 0.81; CA19-9: 0.82). The combined diagnosis of individual or both miRNAs with CA19-9 was more effective for discriminating PC from all controls than the single CA19-9 assay (miR-1290+CA19-9: 0.96, miR-1246+CA19-9: 0.93, miR-1290+miR-1246+CA19-9: 0.97). The abundance of serum miR-1290 and miR-1246 was associated with tumor stage and size respectively and logistic modeling proved that both of them were independent risk factors for PC. : Serum miR-1290 and miR-1246 might be promising biomarkers for PC diagnosis and the combined detection of CA19-9, together with miR-1290 or miR-1246, could improve the diagnostic accuracy of PC.
胰腺癌(PC)是一种高度恶性的肿瘤,目前尚无有效的早期诊断生物标志物。本研究旨在筛选和鉴定血清微小RNA(miRNA)作为PC诊断的非侵入性生物标志物。通过对三个独立的基因表达综合数据库(GEO)数据集进行综合分析,筛选出两个上调的miRNA。然后,采用定量逆转录聚合酶链反应(qRT-PCR)检测120例PC患者、40例良性疾病对照者和40例健康对照者血清中这两种miRNA的表达水平,并分析血清miRNA与临床特征之间的相关性。使用受试者工作特征曲线(ROC)分析比较miRNA与糖类抗原19-9(CA19-9)的诊断效能。通过GEO数据集分析,我们发现PC患者中miR-1290和miR-1246上调。与所有对照相比,PC患者血清中miR-1290和miR-1246的表达水平升高,肿瘤切除后显著降低(所有P<0.001)。miR-1290的曲线下面积(AUC)大于miR-1246和CA19-9(miR-1290:0.91;miR-1246:0.81;CA19-9:0.82)。与单独检测CA19-9相比,miR-1290或miR-1246与CA19-9联合诊断在区分PC与所有对照方面更有效(miR-1290+CA19-9:0.96,miR-1246+CA19-9:0.93,miR-1290+miR-1246+CA19-9:0.97)。血清miR-1290和miR-1246的丰度分别与肿瘤分期和大小相关,逻辑回归模型证明它们都是PC的独立危险因素。血清miR-1290和miR-1246可能是PC诊断中有前景的生物标志物,CA19-9与miR-1290或miR-1246联合检测可提高PC的诊断准确性。