title: EGFR expression is associated with cytoplasmic staining of CXCR4 and predicts poor prognosis in triple-negative breast carcinomas.
abstract: The purpose of the present study was to investigate the significance of C-X-C motif chemokine receptor type 4 (CXCR4) and epidermal growth factor receptors (EGFRs) in triple-negative breast cancer (TNBC). CXCR4 and EGFR expression levels were immunohistochemically determined in 207 primary breast cancer specimens. The associations between receptor expression and clinicopathological characteristics were analyzed, and receptor expression was also assessed as a prognostic factor. In the human MDA-MB-231 TNBC cell line, CXCR4 or EGFR was stably knocked down by short hairpin RNA, and the biological behavior of the cells, including migration, invasion and tumorigenesis, was investigated. The results revealed that TNBC was associated with younger age, higher histological grade and an aggressive phenotype. CXCR4 and EGFR were highly expressed in patients with TNBC, and those with high CXCR4 or EGFR expression exhibited an unfavorable prognosis in terms of disease-free survival and overall survival. In MDA-MB-231 cells, the expression of CXCR4 protein was decreased following EGFR silencing, while CXCR4 knockdown also caused a decrease in EGFR protein levels. The migratory and invasive capabilities of MDA-MB-231 cells were decreased following the knockdown of CXCR4 or EGFR expression. A strong correlation between CXCR4 and EGFR expression was identified in patients with TNBC. The results suggest that elevated expression levels of these two receptors may serve as predictive factors for poor prognosis in patients with TNBC. In addition, tumor proliferation, migration, invasion and tumorigenesis are weakened in MDA-MB-231 cells following suppression of CXCR4 or EGFR expression. Therefore, EGFR and CXCR4 may be potential therapeutic targets for TNBC.
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China; Chang Jiang Scholar's Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Li
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Wen-He
authors.initials: WH
authors.lastname: Huang
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: Wu
authors.affiliation: Chang Jiang Scholar's Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China; Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Cai-Wen
authors.initials: CW
authors.lastname: Du
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China; Chang Jiang Scholar's Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China; Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Shantou, Guangdong 515041, P.R. China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhang
keywords: C-X-C motif chemokine receptor type 4; epidermal growth factor receptor; prognosis; triple-negative breast cancer