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Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

ABSTRACT: Background:Delayed diagnosis is the main obstacle to improve prognosis of non-small cell lung cancer (NSCLC). Novel biomarkers for the diagnosis of NSCLC are urgently needed. This study aimed to identify the specific exosomal miRNAs with diagnostic and prognostic potential in NSCLC patients. Materials and Methods:Transmission electron microscopy (TEM), qNano and western blots were used to characterize the exosomes isolated from the serum of NSCLC patients (n=330) and healthy donors (n=312) by ultracentrifugation. Exosomal miRNAs were profiled by miRNA microarrays and verified by quantitative PCR (qPCR). The diagnostic accuracy was determined by receiver operating characteristic (ROC) analysis. Results:A total of differential 22 miRNAs were screened out based on P < 0.05 and fold difference>2.0 by miRNA microarrays, among which, exosomal miR-5684 and miR-125b-5p were significantly down-regulated in NSCLC patients compared to healthy donors, processing favorable diagnostic efficiency for (early) NSCLC. Importantly, the exosomal miR-125b-5p were associated with metastasis (P < 0.0001), chemotherapeutic effect (P=0.007) and survival (P=0.008). Conclusion:Exosomal miR-5684 and miR-125b-5p levels are significantly down-regulated in NSCLC patients, and serve as the promising diagnostic and prognostic biomarkers for NSCLC.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7592397 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

Zhang Zhijun Z Tang Youyong Y Song Xingguo X Xie Li L Zhao Shuping S Song Xianrang X

Frontiers in oncology 20201014

<h4>Background</h4>Delayed diagnosis is the main obstacle to improve prognosis of non-small cell lung cancer (NSCLC). Novel biomarkers for the diagnosis of NSCLC are urgently needed. This study aimed to identify the specific exosomal miRNAs with diagnostic and prognostic potential in NSCLC patients.<h4>Materials and methods</h4>Transmission electron microscopy (TEM), qNano and western blots were used to characterize the exosomes isolated from the serum of NSCLC patients (n=330) and healthy donor ...[more]

PMID: 33178588

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Project description:Exosomal proteins represent valuable research directions in the liquid biopsy of lung cancer (LC). Immunoglobulin subtypes, immunoglobulin molecules with different domains in variable regions, are products of B cell responses to different tumor antigens and are associated with tumor incidence and development. The plasma of patients with LC should theoretically contain a large number of B cell-derived exosomes that specifically recognize tumor antigens. This paper intended to assess the value of the proteomic screening of plasma exosomal immunoglobulin subtypes for diagnosing non-small cell LC (NSCLC). The plasma exosomes of NSCLC patients and healthy control participants (HCs) were isolated using ultracentrifugation. Label-free proteomics was employed to assess the differentially expressed proteins (DEPs), while the biological characteristics of the DEPs were analyzed using GO enrichment. The immunoglobulin content in the top two fold change (FC) values of the DEPs and the immunoglobulin with the lowest P-value were verified using an enzyme-linked immunosorbent assay (ELISA). The differentially expressed immunoglobulin subtypes verified via ELISA were selected to statistically analyze the receiver operating characteristic curve (ROC), after which the diagnostic values of the NSCLC immunoglobulin subtypes were determined via the ROC area under the curve (AUC). The plasma exosomes of the NSCLC patients contained 38 DEPs, of which 23 were immunoglobulin subtypes, accounting for 60.53%. The DEPs were mainly related to the binding between immune complexes and antigens. The ELISA results showed significant differences between the immunoglobulin heavy variable 4-4 (IGHV4-4) and immunoglobulin lambda variable 1-40 (IGLV1-40) in the LC patients and HCs. Compared with the HCs, the AUCs of IGHV4-4, IGLV1-40, and a combination of the two in diagnosing NSCLC were 0.83, 0.88, and 0.93, respectively, while the AUCs for non-metastatic cancer were 0.80, 0.85, and 0.89. Moreover, their diagnostic values for metastatic cancer compared to non-metastatic cancer displayed AUCs of 0.71, 0.74, and 0.83, respectively. When IGHV4-4 and IGLV1-40 were combined with serum CEA to diagnose LC, the AUC value increased, exhibiting values of 0.95, 0.89, and 0.91 for the NSCLC, non-metastatic, and metastatic groups, respectively. Plasma-derived exosomal immunoglobulins containing IGHV4-4 and IGLV 1-40 domains can provide new biomarkers for diagnosing NSCLC and metastatic patients.

Dataset Information

Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

Publications

Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

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