Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy (NAC) is a standard treatment strategy for patients with locally advanced breast cancer (LABC). However, there are no established predictors of chemosensitivity and survival in LABC patients who undergo NAC. Many studies have demonstrated that exosomes and cytokines are impo...

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Autores principales: Hae Hyun Jung, Ji-Yeon Kim, Eun Yoon Cho, Jung Min Oh, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/ee4c6e9839564abaa39cf6e756281830
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spelling oai:doaj.org-article:ee4c6e9839564abaa39cf6e7562818302021-11-11T15:26:34ZElevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy10.3390/cancers132152602072-6694https://doaj.org/article/ee4c6e9839564abaa39cf6e7562818302021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5260https://doaj.org/toc/2072-6694Neoadjuvant chemotherapy (NAC) is a standard treatment strategy for patients with locally advanced breast cancer (LABC). However, there are no established predictors of chemosensitivity and survival in LABC patients who undergo NAC. Many studies have demonstrated that exosomes and cytokines are important players in intercellular communication between tumors and their environments, and are involved in chemotherapy resistance. Recently, it was reported that cytokines can be packaged into exosomes, but whether exosomal cytokines serve as biomarkers in breast cancer patients is still unclear. In this study, we examined the roles of cytokines in both serum and exosomes as prognostic biomarkers for long-term outcomes in patients with breast cancer who undergo NAC. We isolated exosomes from the blood of 129 patients with early breast cancer who were receiving neoadjuvant chemotherapy between 2008 and 2011 at Samsung Medical Center. The levels of cytokines and growth factors in serum and exosomes were measured with ProcartaPlex immune-related panels. We investigated correlations between clinic-pathologic variables and patient survival, and Cox proportional hazards regression analysis was performed for prognostic evaluation. We detected significant differences in expression patterns between serum cytokines and exosomal cytokines. In both serum and exosomes, many cytokines were positively correlated with age. In univariate analysis, patients with high serum IP-10, serum MMP-1, and exosomal NGF had shorter overall survival. Exosomal NGF showed significantly poorer overall survival in multivariate analysis. These findings suggest that exosomal NGF is useful for identifying patients with poor survival outcomes.Hae Hyun JungJi-Yeon KimEun Yoon ChoJung Min OhJeong Eon LeeSeok Won KimSeok Jin NamYeon Hee ParkJin Seok AhnYoung-Hyuck ImMDPI AGarticleexosomesextracellular vesiclesbreast cancerneoadjuvant chemotherapyprognostic biomarkernerve growth factorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5260, p 5260 (2021)
institution DOAJ
collection DOAJ
language EN
topic exosomes
extracellular vesicles
breast cancer
neoadjuvant chemotherapy
prognostic biomarker
nerve growth factor
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle exosomes
extracellular vesicles
breast cancer
neoadjuvant chemotherapy
prognostic biomarker
nerve growth factor
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Hae Hyun Jung
Ji-Yeon Kim
Eun Yoon Cho
Jung Min Oh
Jeong Eon Lee
Seok Won Kim
Seok Jin Nam
Yeon Hee Park
Jin Seok Ahn
Young-Hyuck Im
Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
description Neoadjuvant chemotherapy (NAC) is a standard treatment strategy for patients with locally advanced breast cancer (LABC). However, there are no established predictors of chemosensitivity and survival in LABC patients who undergo NAC. Many studies have demonstrated that exosomes and cytokines are important players in intercellular communication between tumors and their environments, and are involved in chemotherapy resistance. Recently, it was reported that cytokines can be packaged into exosomes, but whether exosomal cytokines serve as biomarkers in breast cancer patients is still unclear. In this study, we examined the roles of cytokines in both serum and exosomes as prognostic biomarkers for long-term outcomes in patients with breast cancer who undergo NAC. We isolated exosomes from the blood of 129 patients with early breast cancer who were receiving neoadjuvant chemotherapy between 2008 and 2011 at Samsung Medical Center. The levels of cytokines and growth factors in serum and exosomes were measured with ProcartaPlex immune-related panels. We investigated correlations between clinic-pathologic variables and patient survival, and Cox proportional hazards regression analysis was performed for prognostic evaluation. We detected significant differences in expression patterns between serum cytokines and exosomal cytokines. In both serum and exosomes, many cytokines were positively correlated with age. In univariate analysis, patients with high serum IP-10, serum MMP-1, and exosomal NGF had shorter overall survival. Exosomal NGF showed significantly poorer overall survival in multivariate analysis. These findings suggest that exosomal NGF is useful for identifying patients with poor survival outcomes.
format article
author Hae Hyun Jung
Ji-Yeon Kim
Eun Yoon Cho
Jung Min Oh
Jeong Eon Lee
Seok Won Kim
Seok Jin Nam
Yeon Hee Park
Jin Seok Ahn
Young-Hyuck Im
author_facet Hae Hyun Jung
Ji-Yeon Kim
Eun Yoon Cho
Jung Min Oh
Jeong Eon Lee
Seok Won Kim
Seok Jin Nam
Yeon Hee Park
Jin Seok Ahn
Young-Hyuck Im
author_sort Hae Hyun Jung
title Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
title_short Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
title_full Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
title_fullStr Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
title_full_unstemmed Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
title_sort elevated level of nerve growth factor (ngf) in serum-derived exosomes predicts poor survival in patients with breast cancer undergoing neoadjuvant chemotherapy
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/ee4c6e9839564abaa39cf6e756281830
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