Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

2021 ◽  
Author(s):  
Dan Li ◽  
Wenjia Lai ◽  
Di Fan ◽  
Qiaojun Fang
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Breast Cancer Diagnosis ◽  
Extracellular Vesicle ◽  
Detection Methods ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

Extracellular vesicle-derived microRNA biomarkers: goals and pitfalls

2020 ◽  
Vol 2 (1) ◽  
pp. 42-47
Author(s):  
Stefanie Hermann ◽  
Christian Grätz ◽  
Benedikt Kirchner ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Extracellular Vesicle ◽  
Liquid Biopsies

Liquid biopsy-derived extracellular vesicles (EVs) are an auspicious source for transcriptomic biomarker studies. Here, we review the potential of EV microRNAs (miRNAs) biomarkers, exemplary outline commonly used methods to elucidate new biomarker signatures, and pivotally discuss their applicability at present. Keywords: extracellular vesicles, liquid biopsies, transcriptomic biomarkers, microRNAs

scholarly journals Extracellular Vesicles in Liquid Biopsies: Potential for Disease Diagnosis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jialing Liu ◽  
Ye Chen ◽  
Fang Pei ◽  
Chongmai Zeng ◽  
Yang Yao ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Minimally Invasive ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Enzymatic Degradation ◽  
Disease Diagnosis ◽  
Sample Collection ◽  
Liquid Biopsies ◽  
Promising Tool ◽  
Extracellular Environment

Liquid biopsy is conducted through minimally invasive or noninvasive procedures, and the resulting material can be subjected to genomic, proteomic, and lipidomic analyses for early diagnosis of cancers and other diseases. Extracellular vesicles (EVs), one kind of promising tool for liquid biopsy, are nanosized bilayer particles that are secreted by all kinds of cells and that carry cargoes such as lipids, proteins, and nucleic acids, protecting them from enzymatic degradation in the extracellular environment. In this review, we provide a comprehensive introduction to the properties and applications of EVs, including their biogenesis, contents, sample collection, isolation, and applications in diagnostics based on liquid biopsy.

scholarly journals Advances in Breast Cancer Management and Extracellular Vesicle Research, a Bibliometric Analysis

2021 ◽  
Vol 28 (6) ◽  
pp. 4504-4520
Author(s):  
Ramon Handerson Gomes Teles ◽  
Rafael Sussumu Yano ◽  
Nicolas Jones Villarinho ◽  
Ana Sayuri Yamagata ◽  
Ruy Gastaldoni Jaeger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Liquid Biopsies ◽  
Research Production ◽  
Cancer Management ◽  
Breast Cancer Management

Extracellular vesicles transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers.

scholarly journals Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Lin ◽  
Geng-Xi Cai ◽  
Xiang-Ming Zhai ◽  
Xue-Xi Yang ◽  
Min Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Women’S Health ◽  
Women's Health ◽  
Cancer Patients ◽  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Expression Profiles ◽  
Breast Cancer Diagnosis ◽  
Breast Cancer Patients

Breast cancer is the second cause of cancer-associated death among women and seriously endangers women’s health. Therefore, early identification of breast cancer would be beneficial to women’s health. At present, circular RNA (circRNA) not only exists in the extracellular vesicles (EVs) in plasma, but also presents distinct patterns under different physiological and pathological conditions. Therefore, we assume that circRNA could be used for early diagnosis of breast cancer. Here, we developed classifiers for breast cancer diagnosis that relied on 259 samples, including 144 breast cancer patients and 115 controls. In the discovery stage, we compared the genome-wide long RNA profiles of EVs in patients with breast cancer (n=14) and benign breast (n=6). To further verify its potential in early diagnosis of breast cancer, we prospectively collected plasma samples from 259 individuals before treatment, including 144 breast cancer patients and 115 controls. Finally, we developed and verified the predictive classifies based on their circRNA expression profiles of plasma EVs by using multiple machine learning models. By comparing their circRNA profiles, we found 439 circRNAs with significantly different levels between cancer patients and controls. Considering the cost and practicability of the test, we selected 20 candidate circRNAs with elevated levels and detected their levels by quantitative real-time polymerase chain reaction. In the training cohort, we found that BCExoC, a nine-circRNA combined classifier with SVM model, achieved the largest AUC of 0.83 [95% CI 0.77-0.88]. In the validation cohort, the predictive efficacy of the classifier achieved 0.80 [0.71-0.89]. Our work reveals the application prospect of circRNAs in plasma EVs as non-invasive liquid biopsies in the diagnosis and management of breast cancer.

scholarly journals Advanced and futuristic approaches for breast cancer diagnosis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jayanti Mishra ◽  
Bhumika Kumar ◽  
Monika Targhotra ◽  
P. K. Sahoo
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Cancer Diagnosis ◽  
Breast Cancer Diagnosis ◽  
Diagnostic Techniques ◽  
Main Body ◽  
Detection Techniques ◽  
Initial Stage ◽  
Common Causes ◽  
Delay In Treatment

Abstract Background Breast cancer is the most frequent cancer and one of the most common causes of death in women, impacting almost 2 million women each year. Tenacity or perseverance of breast cancer in women is very high these days with an extensive increasing rate of 3 to 5% every year. Along with hurdles faced during treatment of breast tumor, one of the crucial causes of delay in treatment is invasive and poor diagnostic techniques for breast cancer hence the early diagnosis of breast tumors will help us to improve its management and treatment in the initial stage. Main body Present review aims to explore diagnostic techniques for breast cancer that are currently being used, recent advancements that aids in prior detection and evaluation and are extensively focused on techniques that are going to be future of breast cancer detection with better efficiency and lesser pain to patients so that it helps to a physician to prevent delay in treatment of cancer. Here, we have discussed mammography and its advanced forms that are the need of current era, techniques involving radiation such as radionuclide methods, the potential of nanotechnology by using nanoparticle in breast cancer, and how the new inventions such as breath biopsy, and X-ray diffraction of hair can simply use as a prominent method in breast cancer early and easy detection tool. Conclusion It is observed significantly that advancement in detection techniques is helping in early diagnosis of breast cancer; however, we have to also focus on techniques that will improve the future of cancer diagnosis in like optical imaging and HER2 testing.

scholarly journals Genomic instability-derived plasma extracellular vesicle-microRNA signature as a minimally invasive predictor of risk and unfavorable prognosis in breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Siqi Bao ◽  
Ting Hu ◽  
Jiaqi Liu ◽  
Jianzhong Su ◽  
Jie Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Minimally Invasive ◽  
Genomic Instability ◽  
Extracellular Vesicles ◽  
Disease Risk ◽  
Prognostic Indicator ◽  
Mirna Regulation ◽  
Mirna Signature ◽  
Operating Characteristics

Abstract Background Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. Experimental design Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. Results We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. Conclusions We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.

scholarly journals Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250642
Author(s):  
Sarah Hamdy Ahmed ◽  
Nancy A. Espinoza-Sánchez ◽  
Ahmed El-Damen ◽  
Sarah Atef Fahim ◽  
Mohamed A. Badawy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Inflammatory Breast Cancer ◽  
Roc Curves ◽  
Cost Effective ◽  
Extracellular Vesicle ◽  
Lymphatic Invasion ◽  
Precipitation Method ◽  
Liquid Biopsies ◽  
Diagnostic Biomarkers

Inflammatory breast cancer (IBC) is a rare, but aggressive entity of breast carcinoma with rapid dermal lymphatic invasion in young females. It is either poorly or misdiagnosed as mastitis because of the absence of a distinct lump. Small extracellular vesicles (sEVs) circulating in liquid biopsies are a novel class of minimally invasive diagnostic alternative to invasive tissue biopsies. They modulate cancer progression via shuttling their encapsulated cargo including microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. Plasma sEVs < 200 nm were isolated using a modified cost-effective polyethylene glycol (PEG)-based precipitation method and compared to standard methods, namely ultracentrifugation and a commercial kit, where the successful isolation was verified by different approaches. We evaluated the expression levels of selected sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p using quantitative real PCR (qPCR). Relative to non-IBC, our qPCR data showed that sEV-derived miR-181b-5p and miR-222-3p were significantly upregulated, whereas let-7a-5p was downregulated in IBC patients. Interestingly, receiver operating characteristic (ROC) curves analysis revealed that diagnostic accuracy of let-7a-5p alone was the highest for IBC with an area under curve (AUC) value of 0.9188, and when combined with miR-222-3p the AUC was improved to 0.973. Further, 38 hub genes were identified using bioinformatics analysis. Together, circulating sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p serve as promising non-invasive diagnostic biomarkers for IBC.

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