Serum miR-1228-3p and miR-181a-5p as Noninvasive Biomarkers for Non-Small Cell Lung Cancer Diagnosis and Prognosis

• Published in: BioMed research international Vol. 2020; no. 2020; pp. 1 - 13
• Main Authors: Yin, Yunhong, Liu, Xiao, Li, Rui, Zhang, Mengyu, Xue, Wei-Xiao, Qu, Yi-Qing
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; John Wiley & Sons, Inc
• Subjects: Bioinformatics; Biomarkers; Biomarkers, Tumor - blood; Cancer therapies; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - genetics; Computational Biology - methods; Confidence intervals; Diagnosis; Down-Regulation - genetics; Female; Gene expression; Gene Expression Profiling - methods; Genes; Health aspects; Humans; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - blood; Lung Neoplasms - genetics; Male; Medical prognosis; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Non-small cell lung carcinoma; Patients; Polymerase chain reaction; Prognosis; Regression analysis; Reverse transcription; ROC Curve; Small cell lung carcinoma; Statistical analysis; Studies; Up-Regulation - genetics; Taiwan; United States > US; China
• DOI: 10.1155/2020/9601876
• ISSN: 2314-6133; 2314-6141

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.