CXCR4 and CXCR3 are two distinct prognostic biomarkers in breast cancer: Database mining for CXCR family members

CXC chemokine receptors (CXCRs) and chemokines are involved in tissue development and homeostasis, including in cancer development and progression. To date, seven CXCRs have been identified. However, the expression of CXCRs and their influence on the occurrence and development of breast cancer (BC) requires further investigation. In the present study, mRNA expression levels of the seven CXCRs were compared between normal tissues and several cancer types using the Oncomine database. Highly expressed CXCRs were selected and the expression levels of these CXCRs were examined in different subtypes of BC using the Gene Expression-Based Outcome for Breast Cancer database. Finally, the prognostic value of these CXCRs was examined using Kaplan-Meier plotter. It was found that, compared with normal controls, transcripts of CXCR4 and CXCR3 were significantly overexpressed in BC samples compared with other CXCRs. Survival analysis showed that high expression of CXCR4 promoted the recurrence of BC but had no impact on overall survival (OS), while a high level of CXCR3 transcript expression was significantly associated with increased survival in patients with BC. With regards to different subtypes of BC, the present study revealed that high CXCR4 transcript expression was significantly associated with both longer relapse-free survival and OS only in basal-like BC. Furthermore, CXCR4 promoted chemosensitivity in patients with basal-like BC and induced resistance against endocrine therapy for patients with luminal A BC. Thus, CXCR4 and CXCR3 are two distinct prognostic biomarkers and further studies are required.