Plasma miR-324-3p and miR-1285 as diagnostic and prognostic biomarkers for early stage lung squamous cell carcinoma

// Xujie Gao 1, 3, 4 , Yang Wang 1, 3, 4 , Hua Zhao 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, Tianjin, China 2 Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 3 National Clinical Research Center of Cancer, Tianjin, China 4 Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China 5 Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China Correspondence to: Xiubao Ren, email: renxiubao@tjmuch.com Hui Li, email: lihui@tjmuch.com Keywords: lung squamous cell carcinoma, plasma, miRNA, diagnostic marker, prognostic marker Received: April 19, 2016      Accepted: June 30, 2016      Published: August 11, 2016 ABSTRACT Background: Specific biomarkers for early detection and outcome prediction of lung squamous cell carcinoma (LSCC) are still lacking. This study assessed the differentially expressed miRNAs as potential biomarkers for early stage LSCC. Results: Base on the results of multi-phase study, we found that miR-324-3p was significantly up-regulated, whereas mir-1285 was significantly down-regulated in plasma of stage I LSCC patients compared to healthy controls. ROC analysis showed that AUC of miR-324-3p and miR-1285 were 0.79 and 0.85, respectively. The combination of these two miRNAs could further improve the diagnostic accuracy (AUC = 0.89). The multivariate analysis revealed that plasma miR-324-3p level was an independent prognostic predictor for early stage LSCC. Methods: 395 patients and 195 healthy controls were enrolled in this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. We also evaluated the association of candidate miRNAs with overall survival of early stage LSCC patients. Finally, the target genes of the candidate miRNAs were analyzed using public available databases and bioinformatics methods. Conclusions: The current study suggests that plasma miR-324-3p and miR-1285 levels could serve as LSCC early detection markers while miR-324-3p may serve as a prognostic marker for LSCC patients.