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
Journal
Cancers
Journal Volume
13
Journal Issue
3
Date Issued
2021-02-01
Author(s)
Abstract
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. 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; p = 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; p = 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.
Subjects
Biomarker | Brain metastasis | Circulating exosomes | Exosomal integrins | Extracellular vesicles | Whole brain radiotherapy
SDGs
Other Subjects
beta3 integrin; adult; aged; Article; brain dysfunction; brain metastasis; cancer control; cancer growth; cancer patient; cancer prognosis; cancer survival; correlational study; evidence based medicine; female; groups by age; histology; human; incidence; lung cancer; major clinical study; male; neurosurgery; observational study; overall survival; prospective study; scoring system; sex; skull irradiation; stereotactic radiosurgery; whole brain radiotherapy
Type
journal article