A panel of miRNAs derived from plasma extracellular vesicles as novel diagnostic biomarkers of lung adenocarcinoma

Yao, Bing; Qu, Shuang; Hu, Ruifeng; Gao, Wen; Jin, Shidai; Liu, Ming; Zhao, Quan

doi:10.1002/2211-5463.12753

Cited by 31 publications

(17 citation statements)

References 44 publications

(68 reference statements)

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“…hsa-miR-451a has also been shown to have an association with lung cancer. Yao et al (41) demonstrated that hsa-miR-451a derived from extracellular vesicles was significantly increased in plasma of LUAD patients, compared to HCs, and was available for LUAD diagnosis. Especially mentioned, hsa-miR-451a was reported to play a key role in inhibiting the migration and invasion of NSCLC cells by regulating ATF2 expression (42).…”

Section: Discussionmentioning

confidence: 99%

Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma

Chen

Hao

et al. 2022

Front. Oncol.

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BackgroundConsidering the absence of apparent symptoms at the early stage, most patients with lung adenocarcinoma (LUAD) present at an advanced stage, leading to a dismal 5-year survival rate of <20%. Thus, finding perspective non-invasive biomarkers for early LUAD is very essential.MethodsWe developed a fucose-captured strategy based on lentil lectin-magnetic beads to isolate fucosylated exosomes from serum. Then, a prospective study was conducted to define the diagnostic value of serum exosomal miRNAs for early LUAD. A total of 310 participants were enrolled, including 146 LUAD, 98 benign pulmonary nodules (BPNs), and 66 healthy controls (HCs). Firstly, exosome miRNAs in the discovery cohort (n = 24) were profiled by small RNA sequencing. Secondly, 12 differentially expressed miRNAs (DEmiRs) were selected for further screening in a screening cohort (n = 64) by qRT-PCR. Finally, four candidate miRNAs were selected for further validation in a validating cohort (n = 222).ResultsThis study demonstrated the feasibility of a fucose-captured strategy for the isolation of fucosylated exosomes from serum, evidenced with exosomal characteristics identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting, as well as rapid and convenient operation of <10 min. Furthermore, a miRNA panel for early LUAD composed of miR4732-5p, miR451a, miR486-5p, and miR139-3p was defined with an AUC of 0.8554 at 91.07% sensitivity and 66.36% specificity.ConclusionsThe fucose-captured strategy provides a reliable, as well as rapid and convenient, approach for the isolation of tumor-derived exosomes from serum. A four-fucosylated exosomal miRNA panel presents good performance for early LUAD diagnosis.

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Section: Discussionmentioning

confidence: 99%

Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma

Chen

Hao

et al. 2022

Front. Oncol.

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“… MicroRNA Target gene Sample Cancer Refs. ↑ miR-205–5p HSPA8; DNAJA1 Serum EV Ovarian [289] ↑ miR-214–3p HSP90AB1;HSPD1 Serum EV Ovarian [289] ↑ miR-214–5p HSPA2;HSPA14; BAG2 Serum EV Ovarian [289] ↑ miR-495–3p HSPA5; HSPA1B; HSP90AA1; DNAJC21 Plasma EV Lung [290] ↓ miR-411–5p DNAJB9;DNAJC10;ST13 Plasma EV Lung [290] ↓ miR-615–3p HSPA1B;HSPA4;CCT8;HSPA8;HSPA9;CCT1;HSP90AB1;DNAJA2;DNAJC9;DNAJC10; PPIF;CDC37;TRAP1;BAG6;BAG5;CCT7 Plasma EV ccRCC [291] ↑ miR-224–5p HSP90AA1 Serum EV ccRCC [292] ↑ miR-224–3p DNAJB4; DNAJC28 Serum EV ccRCC [292] ↑ miR-375 HSP90AA1;DNAJC8; DNAJC2 Urine EV Prostate [ 293 , 294 ] ↑ Let-7c-5p HSPA4;DNAJC6;DNAJC16; DNAJC28 Urine EV Prostate [294] ↑ Let-7c-3p DNAJB6; BAG4 Urine EV Prostate [294] ↓ miR-196a-5p HSPA4L; TRAP1 Urine EV Prostate [295] ↑ miR-326 HSPA1B …”

Section: Hsps and Micrornasmentioning

confidence: 99%

Extracellular heat shock proteins and cancer: New perspectives

Albakova

Siam

Sacitharan

et al. 2021

Translational Oncology

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Highlights High expression of extracellular heat shock proteins (HSPs) indicates highly aggressive tumors. HSP profiling of extracellular vesicles (EVs) derived from various biological fluids and released by immune cells may open new perspectives for an identification of diagnostic, prognostic and predictive biomarkers of cancer. Identification of specific microRNAs targeting HSPs in EVs may be a promising strategy for the discovery of novel biomarkers of cancer.

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“…The GSE111803 dataset was based on GPL16791 Illumina HiSeq 2500, including ve serum exosome samples of lung adenocarcinoma and ve healthy controls. [11] The GSE90728 based on GPL16791Illumina HiSeq 2500 contained 36 NSCLC tissues and 32 adjacent lung tissue, and 27 LUAD tissues and 24 adjacent lung tissue were included in the present study.…”

Section: Microarray Datamentioning

confidence: 99%

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Bao

Sun²,

Zhang

2022

Preprint

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Background: The immune microenvironment of lung cancer is complex, and T-cell tolerance is a primary mechanism of immune evasion. Tumor-derived exosomes (TEX) miRNAs regulate immune cells in tumor microenvironment (TME), contributing to tumor immune suppression. However, the underlying mechanisms remain unclear.Methods: TEX miRNA expression dataset (GSE111803) and CD8+ T cells mRNA expression profile (GSE90728) in lung adenocarcinoma (LUAD) were downloaded from Gene Expression Omnibus (GEO). The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were analyzed. The intersection of target genes of DEMs and DEGs was defined as the overlapped target genes. We performed the function and pathway analysis for DEGs and the overlapped genes by the DAVID tool and constructed a protein-protein interaction (PPI) network to screen modules and hub genes. Results: In total, 7 DEMs (5 upregulated and two downregulated miRNAs) and 672 DEGs (219 upregulated and 453 downregulated genes) were identified, then 185 overlapped genes for upregulated DEMs were selected for further analysis. GO analysis indicated the DEGs were mainly enriched in positive regulation of B cell activation, innate immune, while the overlapped genes were primarily involved in regulation of immune response. The pathway analysis suggested DEGs were primarily enriched in cytokine-cytokine receptor interaction, while the overlapped genes were primarily enriched in osteoclast differentiation. The PPI network revealed three significant modules for DEGs and the overlapped genes sets. These modules genes were mainly enriched in cell cycle, chemokine signaling pathway, and cytokine-cytokine receptor interaction, respectively.Conclusions: These results preliminarily revealed the mRNA expression profiles and the molecular regulatory mechanism of TEX miRNA regulated tumor immune response in LUAD.

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A panel of miRNAs derived from plasma extracellular vesicles as novel diagnostic biomarkers of lung adenocarcinoma

Cited by 31 publications

References 44 publications

Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma

Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma

Extracellular heat shock proteins and cancer: New perspectives

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

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