Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of lung cancer

摘要

Lung cancer is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, the microarray of miRNAs and mRNAs on the same samples was performed and the intersection taken with The Cancer Genome Atlas (TCGA) lung cancer miRNA/RNAseq dataset. Then, miRNA-mRNA regulatory network was constructed to identify miRNA candidates associated with lung cancer through integrating gene expression and miRNA-target prediction. Furthermore, the expression levels of miRNA candidates were validated by stem-loop real-time reverse transcription PCR (qRT-PCR) in larger lung cancer population. The relationship between signature miRNAs and the risk of lung cancer were assessed by conditional logistic regression analysis. Diagnostic value of these miRNAs was determined by areas under receiver operating characteristic curves (ROC). The Affymetrix microarray analysis identified a total of 116 miRNAs and 502 mRNAs that could distinguish lung tumor tissues from adjacent non-tumor tissues, of which 70 miRNAs and 136 mRNAs were upregulated, while 46 miRNAs and 366 mRNAs were downregulated, respectively. In combination with TCGA analysis, we identified 32 miRNAs and 377 mRNAs related to lung cancer. Then, 28 key miRNAs related to 61 intersection mRNAs were identified by miRNA-mRNA network analysis. The miRNA function analysis was indicative of that 18 upregulated and 10 downregulated miRNAs involved in signaling pathways related to Environmental Information Processing and Human Diseases. Population result showed that the expression of 7 miRNAs (miR-205-5p, miR-3917, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p and miR-27a-5p) was consistent with the analysis result of micro array and TCGA. In addition, upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p, miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734, 0.776, respectively. Therefore, there are a set of signature miRNAs which may be promising biomarkers for the early screening of high-risk populations and early diagnosis of lung cancer.