scholarly journals Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Shona Pedersen ◽  
Katrine Papendick Jensen ◽  
Bent Honoré ◽  
Søren Risom Kristensen ◽  
Camilla Holm Pedersen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Functional Enrichment ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Small Cell Lung

Abstract Background Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection. Methods Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis. Results Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC =  − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67–0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis. Conclusions In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.

scholarly journals Circulating Microvesicles and Exosomes in Small Cell Lung Cancer by Quantitative Proteomics

2021 ◽  
Author(s):  
Shona Pedersen ◽  
Katrine Papendick Jensen ◽  
Bent Honoré ◽  
Søren Risom Kristensen ◽  
Camilla Holm Pedersen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Factor H ◽  
Functional Enrichment ◽  
Healthy Controls ◽  
Small Cell Lung

Abstract Background: Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection.Methods: Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis.Results: Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC = −1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69-0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67-0.97) in SCLC patients compared to heatlhy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis.Conclusions: In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.

scholarly journals Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer

2011 ◽  
Vol 30 (6) ◽  
pp. 407-414 ◽  
Author(s):  
Juan Wei ◽  
Wen Gao ◽  
Cheng-Jun Zhu ◽  
Yi-Qian Liu ◽  
Zhu Mei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Plasma Microrna

scholarly journals 30PD Novel plasma circulating microRNA signature for early detection of non-small cell lung cancer in liquid biopsy

2016 ◽  
Vol 11 (4) ◽  
pp. S68
Author(s):  
T. Powrózek ◽  
P. Krawczyk ◽  
D. Kowalski ◽  
B. Kuźnar-Kamińska ◽  
K. Winiarczyk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Circulating Microrna ◽  
Small Cell Lung

Profiling Tumor-Associated Antibodies for Early Detection of Non-small Cell Lung Cancer

2006 ◽  
Vol 1 (6) ◽  
pp. 513-519 ◽  
Author(s):  
Li Zhong ◽  
Sarah P. Coe ◽  
Arnold J. Stromberg ◽  
Nada H. Khattar ◽  
James R. Jett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Identification of LOC338963 and AP3B2 as Potential Biomarkers for Lambert-Eaton Myasthenic Syndrome

2021 ◽  
Author(s):  
Fei Yang ◽  
Feng Jing ◽  
Yang Li ◽  
Shanshan Kong ◽  
Shimin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.

scholarly journals Loading MicroRNA-376c in Extracellular Vesicles Inhibits Properties of Non-Small Cell Lung Cancer Cells by Targeting YTHDF1

2020 ◽  
Vol 19 ◽  
pp. 153303382097752
Author(s):  
Jianying Zhou ◽  
Dan Xiao ◽  
Tingting Qiu ◽  
Jun Li ◽  
Zhentian Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Rna Binding ◽  
Biological Activities ◽  
Expression Patterns ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Objective: Extracellular vesicles (Evs) secreted from cells have been revealed to mediate signal transduction between cells. Nevertheless, the mechanisms through which molecules transported by EVs function remain to be elucidated. In the present study, the functional relevance of endothelial cells (ECs)-secreted Evs carrying microRNA-376c (miR-376c) in the biological activities of non-small cell lung cancer (NSCLC) cells was investigated, including the related mechanisms. Methods: Two cell lines with the highest YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) expression were selected for subsequent experiments. Cellular proliferation, migration, invasion and apoptosis were measured by EdU, wound healing, Transwell assays and flow cytometry, respectively. The binding relationship between miR-376c and YTHDF1 was analyzed by dual-luciferase reporter assays. The miR-376c, YTHDF1 and β-catenin expression was evaluated by qPCR assays and western blot assays. Results: The expression patterns of YTHDF1 were higher in NSCLC cells, whereas miR-376c was reduced versus the normal bronchial epithelial cells. Silencing of YTHDF1 repressed NSCLC cell proliferation, invasion and migration abilities, whereas enhanced apoptosis. miR-376c negatively modulated YTHDF1 expression. Under co-culture conditions, ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/β-catenin pathway activation. Rescue experiments revealed that YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in NSCLC cells. Conclusion: EC-delivered Evs inhibit YTHDF1 expression and the Wnt/β-catenin pathway induction via miR-376c overexpression, thus inhibiting the malignant phenotypes of NSCLC cells.

Abstract 4568: Multivariate analysis of a panel of protein biomarkers for early detection of non-small cell lung cancer

2010 ◽  
Author(s):  
Charlie Birse ◽  
William M. FitzHugh ◽  
Jenny Heidbrink ◽  
Gulshan Dhariwal ◽  
Douglas A. Bost ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Biomarkers

scholarly journals The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ning An ◽  
Haoyi Wang ◽  
Wenxiao Jia ◽  
Wang Jing ◽  
Chao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
T Lymphocyte ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Proliferation Potential

Abstract Background Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression. Methods This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured. Results CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324–14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = − 0.379; p = 0.0003, r = − 0.464). Conclusion The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS.

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