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Expression of serum exosomal miR-23b-3p in non-small cell lung cancer and its diagnostic efficacy.

ABSTRACT: The present study aimed to investigate the expression of serum exosomal miR-23b-3p in non-small cell lung cancer (NSCLC) and to determine its diagnostic efficacy for NSCLC. From October, 2017 to October, 2019, 80 patients with NSCLC, 60 patients with pneumonia and 30 healthy subjects undergoing physical examination were enrolled at the People's Hospital of Yangzhong City. Serum samples were collected from the 3 groups of patients. The expression of miR-23b-3p in exosomes was detected by RT-qPCR. The Chi-squared test was used to analyze the expression level of miR-23b-3p in exosomes, and the patients with NSCLC were divided into 2 groups according to the expression level. The association between the patient clinicopathological parameters and receiver operating characteristic (ROC) curves was used to evaluate the diagnostic efficacy of serum exosomal miR-23b-3p in NSCLC. The expression level of serum exosomal miR-23b-3p in the patients with NSCLC was significantly higher than that in patients with pneumonia (t=10.332, P<0.001) and healthy subjects (t=12.810, P<0.001); serum exosomal miR-23b-3p was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage (P<0.05). The area under the curve (AUC) for miR-23b-3p was 0.915 (95% CI, 0.84-0.92), the optimal relative expression of miR-23b-3p was 3.46, the sensitivity of diagnosis was 87.4%, and the specificity was 93.8%, all higher than that of carcinoembryonic antigen (CEA). The ROCAUC of NSCLC was 0.645 (95% CI, 0.641-0.772) and for Cyfra21-1 it was 0.745 (95% CI, 0.701-0.812). Compared with the patients with pneumonia and the healthy subjects, the patients with NSCLC exhibited a higher level of serum exosomal miR-23b-3p. On the whole, these findings indicate that miR-23b-3p has a higher clinical diagnostic efficacy and may thus be a potential biomarker for the early diagnosis of NSCLC.

SUBMITTER: Wang J

PROVIDER: S-EPMC7405601 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Expression of serum exosomal miR-23b-3p in non-small cell lung cancer and its diagnostic efficacy.

Wang Jianping J Xue Hengchuan H Zhu Zonghai Z Gao Jie J Zhao Mengmeng M Ma Zhenkai Z

Oncology letters 20200717 4

The present study aimed to investigate the expression of serum exosomal miR-23b-3p in non-small cell lung cancer (NSCLC) and to determine its diagnostic efficacy for NSCLC. From October, 2017 to October, 2019, 80 patients with NSCLC, 60 patients with pneumonia and 30 healthy subjects undergoing physical examination were enrolled at the People's Hospital of Yangzhong City. Serum samples were collected from the 3 groups of patients. The expression of miR-23b-3p in exosomes was detected by RT-qPCR. ...[more]

PMID: 32774503

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Project description:The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543-0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-? signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

Project description: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.

Dataset Information

Expression of serum exosomal miR-23b-3p in non-small cell lung cancer and its diagnostic efficacy.

Publications

Expression of serum exosomal miR-23b-3p in non-small cell lung cancer and its diagnostic efficacy.

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