Identification of a three-miRNA signature as a blood-borne diagnostic marker for early diagnosis of lung adenocarcinoma

// Yang Wang 1, 3, 4, * , Hua Zhao 1, 3, 4, * , Xujie Gao 1, 3, 4 , Feng Wei 1, 3, 4 , Xinwei Zhang 2, 3, 4 , Yanjun Su 3, 5 , Changli Wang 3, 5 , Hui Li 1, 3, 4 , Xiubao Ren 2, 3, 4 1 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China 2 Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China 3 National Clinical Research Center of Cancer, 300060 Tianjin, China 4 Key Laboratory of Cancer Immunology and Biotherapy, 300060 Tianjin, China 5 Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China * These authors contributed equally to this work Correspondence to: Xiubao Ren, e-mail: renxiubao@tjmuch.com Hui Li, e-mail: lihui@tjmuch.com Keywords: lung adenocarcinoma, miRNA, plasma, diagnosis, biomarker Received: January 12, 2016      Accepted: March 14, 2016      Published: March 27, 2016 ABSTRACT Background: The subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed. Results: Based on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer. Methods: Two hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system. Conclusions: Taken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma.