A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer

Oncotarget. 2016 Jun 14;7(24):37250-37259. doi: 10.18632/oncotarget.9363.

Abstract

Introduction: Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy volunteers.

Results: We identified 7 microRNAs separating lung cancer patients from controls. By using RT-qPCR, we validated 6 microRNAs (miR-429, miR-205, miR-200b, miR-203, miR-125b and miR-34b) with a significantly higher abundance in serum from NSCLC patients. Furthermore, the 6 miRNAs were validated in a different dataset, revealing an area under the receiver operating characteristic curve of 0.89 for stage I-IV and 0.88 for stage I/II.

Materials and methods: We profiled the expression of 754 unique microRNAs by TaqMan Low Density Arrays, and analyzed serum from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers from Norway, to explore their potential as diagnostic biomarkers. For validation, we analyzed serum collected from high-risk individuals enrolled in the Valencia branch of the International Early Lung Cancer Action Program screening trial (n=107) in addition to 51 lung cancer patients.

Conclusions: Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies.

Keywords: COPD; biomarker; circulating microRNAs; early detection; lung cancer.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Circulating MicroRNA / blood*
  • Early Detection of Cancer / methods*
  • Female
  • Gene Expression Profiling
  • Healthy Volunteers
  • Humans
  • Lung / pathology
  • Lung Neoplasms / blood*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Norway
  • Pulmonary Disease, Chronic Obstructive / blood*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA