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Analysis of microRNA (miRNA) expression profiles reveals 11 key biomarkers associated with non-small cell lung cancer.

ABSTRACT: Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer cases which cause most of cancer-related deaths globally. However, the results vary largely in different studies due to different platforms and sample sizes. Here, we aim to identify the key miRNAs in the carcinogenesis of NSCLC that might be potential biomarkers for this cancer.Meta-analysis was performed on miRNA profile using seven datasets of NSCLC studies. Furthermore, we predicted and investigated the functions of genes regulated by key miRNAs.Eleven key miRNAs were identified, including 2 significantly upregulated ones (hsa-miR-21-5p and hsa-miR-233-3p) and 9 downregulated ones (hsa-miR-126-3p, hsa-miR-133a-3p, hsa-miR-140-5p, hsa-miR-143-5p, hsa-miR-145-5p, hsa-miR-30a-5p, hsa-miR-30d-3p, hsa-miR-328-3pn, and hsa-miR-451). The functional enrichment analysis revealed that both up- and downregulated miRNAs were proportionally associated with regulation of transcription from RNA polymerase II promoter. According to transcription factor analysis, there were 65 (43.9%) transcription factors influenced by both up- and downregulated miRNAs.In this study, 11 meta-signature miRNAs, as well as their target genes and transcription factors, were found to play significant role in carcinogenesis of NSCLC. These target genes identified in our study may be profitable to diagnosis and prognostic prediction of NSCLC as biomarkers.

SUBMITTER: Wang K

PROVIDER: S-EPMC5606074 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Analysis of microRNA (miRNA) expression profiles reveals 11 key biomarkers associated with non-small cell lung cancer.

Wang Ke K Chen Mingwei M Wu Wei W

World journal of surgical oncology 20170919 1

<h4>Background</h4>Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer cases which cause most of cancer-related deaths globally. However, the results vary largely in different studies due to different platforms and sample sizes. Here, we aim to identify the key miRNAs in the carcinogenesis of NSCLC that might be potential biomarkers for this cancer.<h4>Methods</h4>Meta-analysis was performed on miRNA profile using seven datasets of NSCLC studies. Furthermore, we predicte ...[more]

PMID: 28927412

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Project description:ObjectiveSince the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis.MethodsA GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis.ResultsmiR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p.ConclusionThe plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients.

Project description:Docetaxel has been used as first-line chemotherapy in advanced non-small cell lung carcinoma (NSCLC), but further extensive and effective application is prevented by drug resistance. MicroRNAs (miRNAs) have recently been identified as important posttranscriptional regulators, which are involved in various biological processes. The aim of this study was to identify microRNA expression profiles involved in the development of docetaxel resistance in NSCLC. Here, microarray chip technology was employed to identify miRNA expression profiles in docetaxel-resistant human NSCLC cell line (SPC-A1/docetaxel). Then, the changes of miRNAs expression (>2-fold compared with control SPC-A1 cell line) were testified by quantitative real-time RT-PCR (qRT-PCR) assay. Furthermore, the potential target genes regulated by selected miRNAs were analysed by various target prediction tools. The expression of a total of 52 miRNAs showed significant difference between SPC-A1/docetaxel cells and control SPC-A1 cells (P < 0.01). Six miRNAs (miR-192, 200b, 194, 424, 98 and 212) exhibited more than 2-fold changes in their expression levels, which were validated by qRT-PCR. The expression of three miRNAs (miR-200b, 194 and 212) was significantly down-regulated in SPC-A1/docetaxel cells, while the expression of other three miRNAs (miR-192, 424 and 98) was significantly up-regulated in SPC-A1/docetaxel cells (P < 0.01). Potential target genes controlled by six selected miRNAs were divided into four groups according to various functions: apoptosis and proliferation (71 genes), cell cycle (68 genes), DNA damage (26 genes) and DNA repair (59 genes). The expression of a few target genes in SPC-A1/docetaxel and SPC-A1 cells were further confirmed by qRT-PCR and Western blot. Taken together, the identification of microRNA expression profiles in docetaxel-resistant NSCLC cells could provide a better understanding of mechanisms involved in drug sensitivity or resistance, which would be helpful to develop novel strategies for targeted therapies in chemorefractive NSCLC patients.

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Analysis of microRNA (miRNA) expression profiles reveals 11 key biomarkers associated with non-small cell lung cancer.

Publications

Analysis of microRNA (miRNA) expression profiles reveals 11 key biomarkers associated with non-small cell lung cancer.

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