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Comprehensive analysis of the prognostic value and immune function of chemokine-CXC receptor family members in breast cancer.

Abstract
Recently, immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma. Unfortunately, many breast cancer (BC) patients show low response to ICIs due to the lack of infiltrating immune cells. Previous studies revealed that chemokine-CXC receptors (CXCRs) play a crucial role in leukocyte infiltration and promote cancer cell proliferation, migration, metastasis, and angiogenesis. However, the underlying functions of CXCRs in cancer-immunity cycle remain unclear. In this study, we firstly found that in comparison to normal tissues, BC tissues, especially basal-like BC, showed increased mRNA levels of CXCR3/4/5/6/8, but decreased CXCR1/2/7 expression using UALCAN and TIMER database. Interestingly, it's was found that the mRNA levels of CXCR3/4/5/6 were decreased in lymphocyte depleted of the BC immune subtype. Subsequently, functional enrichment analysis of distinct CXCRs indicated that CXCR3/4/5/6 were strongly associated to immune-related biological functions. Therefore, further analysis using TIMER and TISIDB database suggested that CXCR3/4/5/6 expression were strongly correlated with tumor-infiltrating lymphocytes (TILs) and immune checkpoints in BC. Finally, Kaplan-Meier Plotter analysis indicated that high mRNA expression of CXCR4 predicted worse relapse-free survival (RFS), whereas CXCR3/5/6 indicated better RFS in BC patients. These findings suggest a therapeutic value for CXCR3/4/5/6 in combination with ICIs for the treatment of BC.
AuthorsLijuan Lyu, Yi Zheng, Yun Hong, Meng Wang, Yujiao Deng, Ying Wu, Peng Xu, Si Yang, Shuqian Wang, Jia Yao, Dai Zhang, Yan Guo, Jun Lyu, Zhijun Dai
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 87 Pg. 106797 (Oct 2020) ISSN: 1878-1705 [Electronic] Netherlands
PMID32702599 (Publication Type: Journal Article)
CopyrightCopyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Biomarkers, Tumor
  • Chemokines
  • RNA, Messenger
  • Receptors, CXCR
Topics
  • Biomarkers, Tumor (metabolism)
  • Breast Neoplasms (diagnosis, mortality)
  • Chemokines (metabolism)
  • Databases as Topic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphocytes, Tumor-Infiltrating (immunology)
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Phenotype
  • Prognosis
  • RNA, Messenger (genetics)
  • Receptors, CXCR (genetics)
  • Survival Analysis

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