Dataset Information

Exosomes in Breast Cancer - Mechanisms of Action and Clinical Potential.

ABSTRACT: Extracellular vesicles (EV) are a heterogeneous group of cell-derived membrane vesicles comprising apoptotic bodies, microvesicles, and small EVs also called as exosomes. Exosomes when initially identified were considered as a waste product but the advancement in research techniques have provided insight into the important roles of exosomes in cell-cell communication, various biological processes and diseases, including cancer. As an important component of EVs, exosomes contain various biomolecules such as miRNAs, lipids, and proteins that largely reflect the characteristics of their parent cells. Notably, cancer cells generate and secrete many more exosomes than normal cells. A growing body of evidence suggests that exosomes, as mediators of intercellular cross-talk, play a role in tumorigenesis, cancer cell invasion, angiogenesis, tumor microenvironment (TME) formation, and cancer metastasis. As we gain more insights into the association between exosomes and cancer, the potential of exosomes for clinical use is becoming more intriguing. This review is focused on the role of exosomes in breast cancer, in terms of breast cancer biology, mechanism of action, potential as biomarkers, and therapeutic opportunities.

SUBMITTER: Liu T

PROVIDER: S-EPMC8178200 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Exosomes in Breast Cancer - Mechanisms of Action and Clinical Potential.

Liu Tiantong T Hooda Jagmohan J Atkinson Jennifer M JM Whiteside Theresa L TL Oesterreich Steffi S Lee Adrian V AV

Molecular cancer research : MCR 20210224 6

Extracellular vesicles (EV) are a heterogeneous group of cell-derived membrane vesicles comprising apoptotic bodies, microvesicles, and small EVs also called as exosomes. Exosomes when initially identified were considered as a waste product but the advancement in research techniques have provided insight into the important roles of exosomes in cell-cell communication, various biological processes and diseases, including cancer. As an important component of EVs, exosomes contain various biomolecu ...[more]

PMID: 33627501

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Project description:BackgroundThe situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown.MethodsGene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer.ResultsCOL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways.ConclusionsElevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

Dataset Information

Exosomes in Breast Cancer - Mechanisms of Action and Clinical Potential.

Publications

Exosomes in Breast Cancer - Mechanisms of Action and Clinical Potential.

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