Exosomes as a liquid biopsy for lung cancer

Cui, Sen; Cheng, Zhuoan; Qin, Wenxin; Jiang, Liyan

doi:10.1016/j.lungcan.2017.12.012

Cited by 142 publications

(121 citation statements)

References 69 publications

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“…17 Given that we prospectively isolated and characterized the exosomes from the serum of mCRC or nmCRC patients by TEM, qNano, 21 However, the expression level of has-miR-320 is highly related to the migration and invasion of ovarian cancer. Recent studies have suggested that exosomes could serve as cancer biomarkers since they carry several validated and surrogate non-invasive biomarkers with diagnostic, prognostic, and predictive value.…”

Section: Discussionmentioning

confidence: 99%

Tumor‐derived exosomal miRNA‐320d as a biomarker for metastatic colorectal cancer

Tang

Zhao

Song

et al. 2019

Clinical Laboratory Analysis

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Background To identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC). Materials and Methods Serum exosomes were isolated from patients with metastatic CRC (n = 34) and non‐metastatic CRC (n = 108) by ultracentrifugation and characterized using transmission electron microscopy, qNano, and Western blot. Differential exosomal miRNAs were screened by sequencing and validated by qPCR in metastatic and non‐metastatic CRC patients. Results After sequence analysis, KEGG analysis showed that differential genes were associated with Rap1 signaling pathway and pathways in cancer, 6 upregulated exosomal miRNAs (miR‐224‐5p, miR‐548d‐5p, miR‐200a‐3p, miR‐320d, miR‐200b‐3p, and miR‐1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miR‐27a‐5p) were screened with fold change >1.5, among which miR‐320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miR‐320d could significantly distinguish metastatic from non‐metastatic CRC patients (P = .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miR‐320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC. Conclusion Serum exosomal miR‐320d is a promising non‐invasive diagnostic biomarker for distinguishing metastatic from non‐metastatic CRC.

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Section: Discussionmentioning

confidence: 99%

Tumor‐derived exosomal miRNA‐320d as a biomarker for metastatic colorectal cancer

Tang

Zhao

Song

et al. 2019

Clinical Laboratory Analysis

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“…tdEV comprise of a variety of vesicles secreted or budded of from cancer cells and are known to play an important role in many tumor biological processes . In a previous work we have demonstrated that a subset of tdEV, which expresses both EpCAM and cytokeratin but not CD45 or DNA, can be enriched and enumerated using the CellSearch and their presence was strongly associated with poor overall survival …”

Section: Introductionmentioning

confidence: 99%

Single tube liquid biopsy for advanced non‐small cell lung cancer

Wit

Rossi

Weber

et al. 2019

Intl Journal of Cancer

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The need for a liquid biopsy in non‐small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAMhigh circulating tumor cells (CTC), EpCAMlow CTC, tumor‐derived extracellular vesicles (tdEV) and cell‐free circulating tumor DNA (ctDNA). EpCAMhigh CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAMlow CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAMhigh CTC, 15% had ≥2 EpCAMlow CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAMhigh CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAMlow CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.

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“…Thus, detecting lung cancer at earlier stages could reduce the mortality rates significantly, and hence, new early diagnostic biomarkers are an urgent requisite for NSCLC. Recent studies have suggested that exosomes could serve as cancer biomarkers, as they carry several validated and surrogate noninvasive biomarkers with diagnostic, prognostic, and predictive value . However, the use of exosomes as diagnostic markers has been evaluated in only a few studies focused on extracellular vesicles or exosomal microRNA; some other studies have previously referred to the diagnostic potential of exosomal proteins in NSCLC …”

Section: Discussionmentioning

confidence: 99%

“…The AUC was 0.911 (95% CI, 0.836-0.986) with 85.7% sensitivity and 84.4% specificity ( Figure 4F). 22 However, the use of exosomes as diagnostic markers has been evaluated in only a few studies focused on extracellular vesicles or exosomal microRNA; some other studies have previously referred to the diagnostic potential of exosomal proteins in NSCLC. 23 Given the potential diagnostic role of exosomes in NSCLC, we prospectively isolated and characterized the exosomes from the serum of healthy donors and patients with different clinical stages of NSCLC.…”

Section: Improveddiagnosticcapacityusingcombined Exosomalproteinsanmentioning

confidence: 99%

Tumor‐derived exosomal proteins as diagnostic biomarkers in non‐small cell lung cancer

et al. 2018

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Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor‐derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non‐small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n = 46) and NSCLC patients (n = 125) by ultracentrifugation and were characterized using transmission electron microscopy, qNano, and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups. The exosomal expression levels of alpha‐2‐HS‐glycoprotein (AHSG) and extracellular matrix protein 1 (ECM1) increased significantly in the NSCLC patients compared to the healthy group. Alpha‐2‐HS‐glycoprotein showed diagnostic values with a maximum area under the receiver operating characteristic curve (AUC) as 0.736 for NSCLC vs healthy individuals (P < .0001) and 0.682 for early stage NSCLC vs healthy individuals (P < .01). Extracellular matrix protein 1 showed the diagnostic capacity with AUC values of 0.683 (P < .001) and 0.656 (P < .05) in cancer and early stage NSCLC compared to healthy individuals. When AHSG was combined with ECM1, the AUCs were 0.795 and 0.739 in NSCLC and early stage patients, respectively. Taken together, the combination of AHSG, ECM1, and carcinoembryonic antigen improved the diagnostic potential of NSCLC. The diagnosis values were AUC of 0.938 for NSCLC and 0.911 for early stage NSCLC vs healthy individuals. Our results suggest that novel proteomic signatures found in serum exosomes of NSCLC patients show potential usefulness as diagnostic tools.

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Exosomes as a liquid biopsy for lung cancer

Cited by 142 publications

References 69 publications

Tumor‐derived exosomal miRNA‐320d as a biomarker for metastatic colorectal cancer

Tumor‐derived exosomal miRNA‐320d as a biomarker for metastatic colorectal cancer

Single tube liquid biopsy for advanced non‐small cell lung cancer

Tumor‐derived exosomal proteins as diagnostic biomarkers in non‐small cell lung cancer

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