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

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, b...

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Autores principales:	Li Lin, Geng-Xi Cai, Xiang-Ming Zhai, Xue-Xi Yang, Min Li, Kun Li, Chun-Lian Zhou, Tian-Cai Liu, Bo-Wei Han, Zi-Jia Liu, Mei-Qi Chen, Guo-Lin Ye, Ying-Song Wu, Zhi-Wei Guo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	breast cancer cancer diagnosis extracellular vesicles circular RNA predictive classifier Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/50ad9ab3e5de4ff49af2300129fcc3ff
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spelling	oai:doaj.org-article:50ad9ab3e5de4ff49af2300129fcc3ff2021-11-10T05:39:06ZPlasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis2234-943X10.3389/fonc.2021.752651https://doaj.org/article/50ad9ab3e5de4ff49af2300129fcc3ff2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.752651/fullhttps://doaj.org/toc/2234-943XBreast 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.Li LinGeng-Xi CaiGeng-Xi CaiXiang-Ming ZhaiXue-Xi YangMin LiKun LiChun-Lian ZhouTian-Cai LiuBo-Wei HanZi-Jia LiuMei-Qi ChenGuo-Lin YeYing-Song WuZhi-Wei GuoFrontiers Media S.A.articlebreast cancercancer diagnosisextracellular vesiclescircular RNApredictive classifierNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer cancer diagnosis extracellular vesicles circular RNA predictive classifier Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	breast cancer cancer diagnosis extracellular vesicles circular RNA predictive classifier Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Li Lin Geng-Xi Cai Geng-Xi Cai Xiang-Ming Zhai Xue-Xi Yang Min Li Kun Li Chun-Lian Zhou Tian-Cai Liu Bo-Wei Han Zi-Jia Liu Mei-Qi Chen Guo-Lin Ye Ying-Song Wu Zhi-Wei Guo Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
description	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.
format	article
author	Li Lin Geng-Xi Cai Geng-Xi Cai Xiang-Ming Zhai Xue-Xi Yang Min Li Kun Li Chun-Lian Zhou Tian-Cai Liu Bo-Wei Han Zi-Jia Liu Mei-Qi Chen Guo-Lin Ye Ying-Song Wu Zhi-Wei Guo
author_facet	Li Lin Geng-Xi Cai Geng-Xi Cai Xiang-Ming Zhai Xue-Xi Yang Min Li Kun Li Chun-Lian Zhou Tian-Cai Liu Bo-Wei Han Zi-Jia Liu Mei-Qi Chen Guo-Lin Ye Ying-Song Wu Zhi-Wei Guo
author_sort	Li Lin
title	Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
title_short	Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
title_full	Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
title_fullStr	Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
title_full_unstemmed	Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis
title_sort	plasma-derived extracellular vesicles circular rnas serve as biomarkers for breast cancer diagnosis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/50ad9ab3e5de4ff49af2300129fcc3ff
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Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis

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