A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients

EBioMedicine. 2015 Aug 4;2(10):1377-85. doi: 10.1016/j.ebiom.2015.07.034. eCollection 2015 Oct.

Abstract

Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT-qPCR confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 were significantly elevated in patients compared to controls. The areas under the curve (AUCs) of the ROC curve of this five-serum miRNA panel were 0.976 (95% CI, 0.939-1.0; P < 0.0001) and 0.823 (95% CI, 0.75-0.896; P < 0.0001) for the two confirmation sets, respectively. In the blind trial, the panel correctly classified 95% NSCLC cases and 84% controls from the American cohort. Most importantly, the panel was capable of distinguishing NSCLC from benign nodules with an AUC of 0.979 (95% CI, 0.959-1.0) in the American cohort and allowed correct prediction of 86% and 95% stage I-II tumors in the Chinese and American cohorts, respectively. This serum miRNA panel holds the potential for diagnosing ethnically diverse NSCLC patients.

Keywords: AUC, the area under the ROC curve; Biomarker; Cq, quantification cycle; Diagnosis; Multicentric; Multiethnic; NSCLC, non-small-cell lung cancer; Non-small-cell lung cancer; RT-qPCR, quantitative reverse transcription polymerase chain reaction; Serum microRNAs; TLDA, TaqMan Low-Density Array; TNM, tumor–node–metastasis; miRNA, microRNA.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling*
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics*
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • ROC Curve
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors

Substances

  • MicroRNAs