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Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor

BACKGROUND: CC-chemokine receptor seven (CCR7), a G-protein coupled receptor normally facilitating immune cells lymphatic homing, has recently been identified on several cancer cells in promoting invasion and lymphatic specific metastasis by mimicking normal leukocytes. As tyrosine kinase inhibitors...

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Autores principales: Xia, Yu, Liu, Li, Xiong, Ying, Bai, Qi, Wang, Jiajun, Xi, Wei, Qu, Yang, Xu, Jiejie, Guo, Jianming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259971/
https://www.ncbi.nlm.nih.gov/pubmed/28114889
http://dx.doi.org/10.1186/s12885-017-3065-3
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author Xia, Yu
Liu, Li
Xiong, Ying
Bai, Qi
Wang, Jiajun
Xi, Wei
Qu, Yang
Xu, Jiejie
Guo, Jianming
author_facet Xia, Yu
Liu, Li
Xiong, Ying
Bai, Qi
Wang, Jiajun
Xi, Wei
Qu, Yang
Xu, Jiejie
Guo, Jianming
author_sort Xia, Yu
collection PubMed
description BACKGROUND: CC-chemokine receptor seven (CCR7), a G-protein coupled receptor normally facilitating immune cells lymphatic homing, has recently been identified on several cancer cells in promoting invasion and lymphatic specific metastasis by mimicking normal leukocytes. As tyrosine kinase inhibitors for metastatic renal cell carcinoma (mRCC) mostly emphasized on vascular inhibition, whether the CCR7 expressing tumor cells with potential lymphatic invasion function could have an impact on mRCC patient’s drug response and survival, was unknown. METHODS: In this study, in a clinical aspect, we retrospectively investigated the prognostic and predictive impact of tumoral CCR7 expression in 110 mRCC patients treated with sunitinib and sorafenib, and its correlation with pre- or post-administration lymphatic involvement. Immunohistochemistry on tissue microarrays were conducted for CCR7 expression evaluation. RESULTS: Kaplan-Meier and univariate analyses suggested high tumoral CCR7 expression as an adverse prognosticator for mRCC patients’ overall survival (OS), which was further confirmed in the multivariate analyses (P = 0.002, P = 0.003 for bootstrap). This molecule could be combined with Heng’s risk model for better patient OS prediction. High tumoral CCR7 expression was also an independent dismal predictor for patients’ progression free survival (PFS) (P = 0.010, P = 0.013 for bootstrap), and correlated with poorer best drug response. Moreover, a possible correlation of CCR7 high expression and patients’ baseline and post-administration lymph node metastasis was found. CONCLUSIONS: High tumoral CCR7 expression correlated with potential lymphatic involvement and poor prognosis of mRCC patients treated with tyrosine kinase inhibitors. Further external validations and basic researches were needed to confirm these results. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3065-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-52599712017-01-26 Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor Xia, Yu Liu, Li Xiong, Ying Bai, Qi Wang, Jiajun Xi, Wei Qu, Yang Xu, Jiejie Guo, Jianming BMC Cancer Research Article BACKGROUND: CC-chemokine receptor seven (CCR7), a G-protein coupled receptor normally facilitating immune cells lymphatic homing, has recently been identified on several cancer cells in promoting invasion and lymphatic specific metastasis by mimicking normal leukocytes. As tyrosine kinase inhibitors for metastatic renal cell carcinoma (mRCC) mostly emphasized on vascular inhibition, whether the CCR7 expressing tumor cells with potential lymphatic invasion function could have an impact on mRCC patient’s drug response and survival, was unknown. METHODS: In this study, in a clinical aspect, we retrospectively investigated the prognostic and predictive impact of tumoral CCR7 expression in 110 mRCC patients treated with sunitinib and sorafenib, and its correlation with pre- or post-administration lymphatic involvement. Immunohistochemistry on tissue microarrays were conducted for CCR7 expression evaluation. RESULTS: Kaplan-Meier and univariate analyses suggested high tumoral CCR7 expression as an adverse prognosticator for mRCC patients’ overall survival (OS), which was further confirmed in the multivariate analyses (P = 0.002, P = 0.003 for bootstrap). This molecule could be combined with Heng’s risk model for better patient OS prediction. High tumoral CCR7 expression was also an independent dismal predictor for patients’ progression free survival (PFS) (P = 0.010, P = 0.013 for bootstrap), and correlated with poorer best drug response. Moreover, a possible correlation of CCR7 high expression and patients’ baseline and post-administration lymph node metastasis was found. CONCLUSIONS: High tumoral CCR7 expression correlated with potential lymphatic involvement and poor prognosis of mRCC patients treated with tyrosine kinase inhibitors. Further external validations and basic researches were needed to confirm these results. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3065-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-23 /pmc/articles/PMC5259971/ /pubmed/28114889 http://dx.doi.org/10.1186/s12885-017-3065-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Xia, Yu
Liu, Li
Xiong, Ying
Bai, Qi
Wang, Jiajun
Xi, Wei
Qu, Yang
Xu, Jiejie
Guo, Jianming
Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title_full Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title_fullStr Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title_full_unstemmed Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title_short Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
title_sort prognostic value of cc-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259971/
https://www.ncbi.nlm.nih.gov/pubmed/28114889
http://dx.doi.org/10.1186/s12885-017-3065-3
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