Detection of circulating exosomal miR-17-5p serves as a novel non-invasive diagnostic marker for non-small cell lung cancer patients

Zhang, Yi; Zhang, Yingmei; Yin, Yunhong; Li, Shuhai

doi:10.1016/j.prp.2019.152466

Cited by 76 publications

(43 citation statements)

References 31 publications

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“…In this study, the authors built a four-molecule panel that included miR-17-5p in combination with three circulating tumor markers, which are the carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and squamous cell carcinoma antigen (SCCA). The diagnostic performance of this panel was verified, and the ROC analysis demonstrated an AUC of 0.860 (95% CI = 0.802 to 0.906, sensitivity = 63%, and specificity = 93%) and 0.844 (95% CI = 0.766 to 0.904, sensitivity = 76%, and specificity = 77%) in the training and validation sets, respectively [83].…”

Section: Exosomesmentioning

confidence: 87%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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Section: Exosomesmentioning

confidence: 87%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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“…Interestingly, no differences were detected in the plasma of the two groups, showing no correlations of levels between plasma and serum. Conversely, exosomal miR-17-5p expression was significantly upregulated in NSCLC patients compared with healthy controls [93] .…”

Section: Lung Cancermentioning

confidence: 89%

The power of microRNAs as diagnostic and prognostic biomarkers in liquid biopsies

Quirico¹,

Orso²

2020

CDR

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In the last decades, progresses in medical oncology have ameliorated the treatment of patients and their outcome. However, further improvements are still necessary, in particular for certain types of tumors such as pancreatic, gastric, and lung cancer as well as acute myeloid leukemia where early detection and monitoring of the disease are crucial for final patient outcome. Liquid biopsy represents a great advance in the field because it is less invasive, less time-consuming, and safer compared to classical biopsies and it can be useful to monitor the evolution of the disease as well as the response of patients to therapy. Liquid biopsy allows the detection of circulating tumor cells, nucleic acids, and exosomes not only in blood but also in different biological fluids: urine, saliva, pleural effusions, cerebrospinal fluid, and stool. Among the potential biomarkers detectable in liquid biopsies, microRNAs (miRNAs) are gaining more and more attention, since they are easily detectable, quite stable in biological fluids, and show high sensitivity. Many data demonstrate that miRNAs alone or in combination with other biomarkers could improve the diagnostic and prognostic power for many different tumors. Despite this, standardization of methods, sample preparation, and analysis remain challenging and a huge effort should be made to address these issues before miRNA biomarkers can enter the clinic. This review summarizes the main findings in the field of circulating miRNAs in both solid and hematological tumors. MIRNAS AS POTENTIAL BIOMARKERSRecently, biomarker research has focused on RNA molecules circulating in the body fluids. RNA analysis is highly sensitive and specific, cheaper than protein analysis, and offers a more dynamic view of cell regulation and states compared to DNA [9] . Long RNA species, however, can be easily degraded by RNAse activity, while shorter RNA molecules, as small non-coding RNAs, are more stable and highly expressed in the blood of cancer patients [10,11] . miRNAs are small non-coding RNAs (19-22 nucleotides) originally discovered in Caenorhabditis elegans in 1993 [12] . In the last decades, miRNAs have been described in all animal models, and some of them resulted

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“…Further studies have demonstrated that miR-761 promotes the progression and metastasis of non-small cell lung cancer by targeting ING4 and TIMP2. Zhang et al (2019) analyzed the expression profiles of several miRNAs in 43 pairs of serum samples and found that the expression of miR-17-5p was significantly up-regulated in patients with NSCLC, suggesting that miR-17-5p has important clinical value in the prediction of NSCLC. Yang et al (2018) showed that the expression level of miR-93-5p was up-regulated in NSCLC and was significantly associated with the overall survival rate of NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Combining with the global triple network, we constructed the ceRNA modules among lncRNAs, co-expressed mRNAs and interacting miRNAs (Figures 5A-C). We discovered that lncRNA EPB41L4A-AS1 could interacted with four miRNAs (miR-761, miR-17-5p, miR-93-5p, miR-106b-5p) ( Table 3 and Figure 5A), which were reported to be highly associated with lung cancer (Yan et al, 2015;Wei et al, 2017;Yang et al, 2018;Zhang et al, 2019). For the other two lncRNAs, lncRNA KB-1732A1.1, and lncRNA RP11-390P2.4, the miRNAs of the subnetwork were reported to be involved in the regulation of lung cancer (Li et al, 2017;Yang et al, 2018;Xiao, 2019) (Figures 5B,C).…”

Section: Topological Analysis Of Lung Cancer Related Lncrna-mrna Networkmentioning

confidence: 99%

Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network Identified lncRNA EPB41L4A-AS1 as a Potential Biomarker in Non-small Cell Lung Cancer

Wang

Zheng

et al. 2020

Front. Genet.

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Background: Recent evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to modulate mRNAs expression by sponging microRNAs (miRNAs). However, the specific mechanism and function of lncRNA-miRNA-mRNA regulatory network in non-small cell lung cancer (NSCLC) remains unclear. Materials and Methods: We constructed a lung cancer related lncRNA-mRNA network (LCLMN) by integrating differentially expressed genes (DEGs) with miRNAtarget interactions. We further performed topological feature analysis and random walk with restart (RWR) analysis of LCLMN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the target DEGs in LCLMN. The expression levels of significant lncRNAs in NSCLC were validated by quantitative real-time PCR (RT-qPCR). The prognostic value of the potential lncRNA was evaluated by Kaplan-Meier analysis. Results: A total of 33 lncRNA nodes, 580 mRNA nodes and 2105 edges were identified from LCLMN. Based on functional enrichment analysis and co-expression analysis, lncRNA EPB41L4A-AS1 was demonstrated to be correlated with the tumorigenesis of NSCLC. RT-qPCR results confirmed that the expression levels of lncRNA EPB41L4A-AS1 in NSCLC tissues were downregulated compared with adjacent non-cancerous tissues. Kaplan-Meier analysis showed that high expression of lncRNA EPB41L4A-AS1 was associated with better overall survival (OS) in NSCLC patients. Further investigation

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Detection of circulating exosomal miR-17-5p serves as a novel non-invasive diagnostic marker for non-small cell lung cancer patients

Cited by 76 publications

References 31 publications

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

The power of microRNAs as diagnostic and prognostic biomarkers in liquid biopsies

Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network Identified lncRNA EPB41L4A-AS1 as a Potential Biomarker in Non-small Cell Lung Cancer

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