Whole blood microRNA expression may not be useful for screening non-small cell lung cancer

• Published in: PloS one Vol. 12; no. 7; p. e0181926
• Main Authors: Patnaik, Santosh K, Kannisto, Eric D, Mallick, Reema, Vachani, Anil, Yendamuri, Sai
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-07-2017; Public Library of Science (PLoS)
• Subjects: Acute coronary syndromes; Adult; Aged; Aged, 80 and over; Bayesian analysis; Benign; Bioinformatics; Biology and life sciences; Biomarkers; Biomarkers, Tumor - blood; Blood; Blood coagulation tests; Cancer; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnosis; Case-Control Studies; Cigarette smoking; Control methods; Diagnosis; Diagnostic systems; DNA microarrays; Empirical analysis; Female; Gene expression; Health risks; Hemoglobin; Humans; Lung cancer; Lung diseases; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Male; Medical diagnosis; Medical screening; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNA; Non-small cell lung cancer; Non-small cell lung carcinoma; Oligonucleotide Array Sequence Analysis; Polymerase chain reaction; Properties; Reproducibility of Results; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Reverse transcription; Ribonucleic acid; RNA; Sensitivity and Specificity; Smoking; Statistical analysis; Statistical tests; Studies; Support vector machines; Surgery; Thoracic surgery; New York; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181926

At least seven studies have suggested that microRNA levels in whole blood can be diagnostic for lung cancer. We conducted a large bi-institutional study to validate this. Qiagen® PAXgene™ Blood miRNA System was used to collect blood and extract RNA from it for 85 pathologic stage I-IV non-small cell lung cancer (NSCLC) cases and 76 clinically-relevant controls who had a benign pulmonary mass, or a high risk of developing lung cancer because of a history of cigarette smoking or age >60 years. Cases and controls were similar for age, gender, race, and blood hemoglobin and leukocyte but not platelet levels (0.23 and 0.26 million/μl, respectively; t test P = 0.01). Exiqon® MiRCURY™ microarrays were used to quantify microRNAs in RNA isolates. Quantification was also performed using Taqman™ microRNA reverse transcription (RT)-PCR assays for five microRNAs whose lung cancer-diagnostic potential had been suggested in seven published studies. Of the 1,941 human mature microRNAs detectable with the microarray platform, 598 (31%) were identified as expressed and reliably quantified among the study's subjects. However, none of the microRNAs was differentially expressed between cases and controls (P >0.05 at false discovery rate <5% in test using empirical Bayes-moderated t statistics). In classification analyses with leave-one-out internal cross-validation, cases and controls could be identified by microRNA expression with 47% and 50% accuracy with support vector machines and top-scoring pair methods, respectively. Cases and controls did not differ for RT-PCR-based measurements of any of the five microRNAs whose biomarker potential had been suggested by seven previous studies. Additionally, no difference for microRNA expression was noticed in microarray-based microRNA profiles of whole blood of 12 stage IA-IIIB NSCLC cases before and three-four weeks after tumor resection. These findings show that whole blood microRNA expression profiles lack diagnostic value for high-risk screening of NSCLC, though such value may exist for selective sub-groups of NSCLC and control populations.