Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study
Brain metastasis (BM) is a major problem in patients with cancer. Exosomes or extracellular vesicles (EV) and integrins contribute to the development of BM, and exosomal integrins have been shown to determine organotropic metastasis. We hypothesized that circulating EV integrins are able to influenc...
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doaj-a6c9054dd3094039a21660dd0a885cb12021-01-21T00:05:35ZengMDPI AGCancers2072-66942021-01-011338038010.3390/cancers13030380Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational StudyGuann-Yiing Chen0Jason Chia-Hsien Cheng1Ya-Fang Chen2James Chih-Hsin Yang3Feng-Ming Hsu4Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, TaiwanDivision of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, TaiwanDepartment of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu 300, TaiwanGraduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, TaiwanDivision of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, TaiwanBrain metastasis (BM) is a major problem in patients with cancer. Exosomes or extracellular vesicles (EV) and integrins contribute to the development of BM, and exosomal integrins have been shown to determine organotropic metastasis. We hypothesized that circulating EV integrins are able to influence the failure patterns and outcomes in patients treated for BM. We prospectively enrolled 75 lung cancer patients with BM who received whole brain radiotherapy (WBRT). We isolated and quantified their circulating EV integrins, and analyzed the association of EV integrins with clinical factors, survival, and intracranial/extracranial failure. Circulating EV integrin levels were independent of age, sex, histology, number of BM, or graded prognostic assessment score. Age, histology, and graded prognostic assessment score correlated with survival. Patients with higher levels of circulating EV integrin β3 had worse overall survival (hazard ratio: 1.15 per 1 ng/mL increase; <i>p</i> = 0.04) following WBRT. Multivariate regression analysis also showed a higher cumulative incidence of intracranial failure (subdistribution hazard ratio: 1.216 per 1 ng/mL increase; <i>p</i> = 0.037). In conclusion, circulating EV integrin β3 levels correlated with survival and intracranial control of patients with lung cancer after WBRT for BM. This supports that EV integrin β3 mediates a brain-tropic metastasis pattern, and may serve as a novel prognostic biomarker for BM.https://www.mdpi.com/2072-6694/13/3/380brain metastasiswhole brain radiotherapycirculating exosomesexosomal integrinsextracellular vesiclesbiomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guann-Yiing Chen Jason Chia-Hsien Cheng Ya-Fang Chen James Chih-Hsin Yang Feng-Ming Hsu |
spellingShingle |
Guann-Yiing Chen Jason Chia-Hsien Cheng Ya-Fang Chen James Chih-Hsin Yang Feng-Ming Hsu Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study Cancers brain metastasis whole brain radiotherapy circulating exosomes exosomal integrins extracellular vesicles biomarker |
author_facet |
Guann-Yiing Chen Jason Chia-Hsien Cheng Ya-Fang Chen James Chih-Hsin Yang Feng-Ming Hsu |
author_sort |
Guann-Yiing Chen |
title |
Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study |
title_short |
Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study |
title_full |
Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study |
title_fullStr |
Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study |
title_full_unstemmed |
Circulating Exosomal Integrin β3 Is Associated with Intracranial Failure and Survival in Lung Cancer Patients Receiving Cranial Irradiation for Brain Metastases: A Prospective Observational Study |
title_sort |
circulating exosomal integrin β3 is associated with intracranial failure and survival in lung cancer patients receiving cranial irradiation for brain metastases: a prospective observational study |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-01-01 |
description |
Brain metastasis (BM) is a major problem in patients with cancer. Exosomes or extracellular vesicles (EV) and integrins contribute to the development of BM, and exosomal integrins have been shown to determine organotropic metastasis. We hypothesized that circulating EV integrins are able to influence the failure patterns and outcomes in patients treated for BM. We prospectively enrolled 75 lung cancer patients with BM who received whole brain radiotherapy (WBRT). We isolated and quantified their circulating EV integrins, and analyzed the association of EV integrins with clinical factors, survival, and intracranial/extracranial failure. Circulating EV integrin levels were independent of age, sex, histology, number of BM, or graded prognostic assessment score. Age, histology, and graded prognostic assessment score correlated with survival. Patients with higher levels of circulating EV integrin β3 had worse overall survival (hazard ratio: 1.15 per 1 ng/mL increase; <i>p</i> = 0.04) following WBRT. Multivariate regression analysis also showed a higher cumulative incidence of intracranial failure (subdistribution hazard ratio: 1.216 per 1 ng/mL increase; <i>p</i> = 0.037). In conclusion, circulating EV integrin β3 levels correlated with survival and intracranial control of patients with lung cancer after WBRT for BM. This supports that EV integrin β3 mediates a brain-tropic metastasis pattern, and may serve as a novel prognostic biomarker for BM. |
topic |
brain metastasis whole brain radiotherapy circulating exosomes exosomal integrins extracellular vesicles biomarker |
url |
https://www.mdpi.com/2072-6694/13/3/380 |
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