CXCR7, a Prognostic Biomarker in Cervical Squamous Cell Carcinoma, May Be a Screening Index for Treatment Options at Stages IB1 and IIA1

PURPOSE: Recent studies indicate that CXC chemokine receptor type 7 (CXCR7) is associated with tumorigenesis, progression, and metastasis of various cancers, but its roles and molecular mechanisms of action in cervical squamous cell carcinoma (CSCC) remain unclear. Our purpose was to explore the expression patterns of CXCR7 and epidermal growth factor receptor (EGFR) in CSCC and to identify possible correlations with clinical characteristics. We also tested whether CXCR7 can be a screening index for treatment options for CSCC stages IB1 and IIA1. METHODS: Expression of CXCR7 and EGFR in tumors from 165 patients with CSCC was evaluated by immunohistochemistry and compared with the clinical data including survival. RESULTS: Patients at CSCC stages IB1 and IIA1 received different treatment options, including radical hysterectomy, pelvic lymph node dissection, and para-aortic lymph node sampling (RH group, 67 patients) or pelvic external-beam radiation therapy with brachytherapy (EBRT group, 34 patients). Disease-free survival (DFS) and overall survival (OS) were compared between two groups at different CXCR7 expression levels. Immunohistochemical staining showed that CXCR7, EGFR, phospho-ERK, and phospho-AKT amounts increased from normal cervical epithelia and cervical intraepithelial neoplasia to CSCC, and CXCR7 was associated with the disease stage, lymph node metastasis, tumor size ≥40 mm, and EGFR expression. Kaplan–Meier analysis revealed that CXCR7 and EGFR expression was associated with shorter DFS and OS. Multivariate analysis suggested that CXCR7 was independently associated with DFS and OS. Prevalence of recurrence and distant metastasis was significantly lower in the EBRT group than in the RH group during CXCR7 expression. Besides, CXCR7 knockdown significantly decreased the proliferation and invasion of CSCC cells. CONCLUSION: CXCR7 is coexpressed with EGFR, which may be involved in ERK or AKT pathway activation. CXCR7 may be a screening index for treatment options at CSCC stages IB1 and IIA1.