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

// Ann Rita Halvorsen 1 , Maria Bjaanæs 1, 2 , Marissa LeBlanc 3 , Are M. Holm 4 , Nils Bolstad 5 , Luis Rubio 6 , Juan Carlos Peñalver 7 , José Cervera 8 , Julia Cruz Mojarrieta 9 , Jose Antonio López-Guerrero 6 , Odd Terje Brustugun 1, 2 , Åslaug Helland 1, 2 1 Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway 2 Department of Oncology, OUS Radiumhospitalet, Oslo, Norway 3 Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway 4 Department of Respiratory Medicine, OUS Rikshospitalet, Oslo, Norway 5 Department of Medical Biochemistry, OUS Radiumhospitalet, Oslo, Norway 6 Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain 7 Department of Thoracic Surgery, Fundación Instituto Valenciano de Oncología, Valencia, Spain 8 Department of Radiology, Fundación Instituto Valenciano de Oncología, Valencia, Spain 9 Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain Correspondence to: Åslaug Helland, email: ahelland@medisin.uio.no Keywords: circulating microRNAs, biomarker, lung cancer, early detection, COPD Received: February 15, 2016 Accepted: April 16, 2016 Published: May 14, 2016 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. Conclusion: Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies.