Concomitant CXCR4 and CXCR7 Expression Predicts Poor Prognosis in Renal Cancer
C. D'Alterio, C. Consales, M. Polimeno, R. Franco, L. Cindolo, L. Portella, M. Cioffi, R. Calemma, L. Marra, L. Claudio, S. Perdona, S. Pignata, G. Facchini, G. Carteni, N. Longo, L. Pucci, A. Ottaiano, S. Costantini, G. Castello and S. Scala
Affiliation: Oncological Immunology Department, National Cancer Institute, Naples, Via M. Semmola, 80131, Naples, Italy.
Keywords: CXCR4, CXCR7, disease free survival, molecular target, prognosis, renal cell carcinoma, disease, molecular, renal, CXCL12, RT- PCR, CXC chemokine, hematopoietic cells, transmembrane receptor, Furhman's grade, HIF-1alpha, CT scan, Real Time-PCR, MCF7 breast cancer cell line, metastatic, RCC, VEGF, PDGF, MAPKp42/44, Lymph nodal status, immunoblotting, flow cytometry, MAPKinase, anti-HIV drugs, T140, bicyclam AMD3100, CCX733, CCX266, siRNA
CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind the CXCR7 receptor also, a recently deorphanized chemokine receptor whose signalling pathway and function are still controversial. This study was conducted to determine patients clinic-pathological factors and outcome according to the expressions of CXCR4 and CXCR7 in renal cell carcinoma (RCC). CXCR4 and CXCR7 expression were evaluated in 223 RCC patients through immunohistochemistry; moreover CXCR4 and CXCR7 were detected in 49 other consecutive RCC patients through RT- PCR. CXCR4 expression was low in 42/223 RCC (18,8%), intermediate in 71/223 (31,9%) and high in 110/223 (49,3%). CXCR7 expression was low in 44/223 RCC patients (19,8%), intermediate in 65/223 (29,1%) and high in 114/223 (51,1%). High CXCR4 and high CXCR7 expression predicted shorter disease free survival. In multivariate analysis, high CXCR4 expression (p= 0.0061), high CXCR7 (p= 0.0194) expression and the concomitant high expression of CXCR4 and CXCR7 (p= 0.0235) are independent prognosis factors. Through RT-PCR, CXCR4 was overexpressed in 36/49 and CXCR7 in 33/49 samples correlating with symptoms at diagnosis and lymph nodes status. So we can hypothesize that CXCR4 and CXCR7, singularly evaluated and in combination, are valuable prognostic factors in RCC patients.
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