Concomitant CXCR4 and CXCR7 Expression Predicts Poor Prognosis in Renal Cancer

Abstract

CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind also the CXCR7 receptor, 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 was evaluated in 223 RCC patients through immunohistochemistry; moreover CXCR4 and CXCR7 was detected in 49 others consecutive RCC patients trough 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.

CXCR4 over-expression and survival in cancer: A system review and meta-analysis

“…Meta-influence analysis did not suggest undue influence of any single study. Although five studies appeared to be outliers [8, 25, 63, 66, 77], we did not find clinical heterogeneity justifying their exclusion. Subsidiary analyses were carried out in the analysis of PFS (Figure 2B).…”

“…Forty-seven studies, with a total of 5,592 patients, included data on progress free survival in 12 types of cancer 8, 10, 12, 14-27, 31-33, 35, 38-40, 43, 45-48, 53, 56, 63-66, 70, 73, 75, 77-80, 82, 83, 85, 88, 89]. Of all the participants, 2583 (46%) were CXCR4 over-expression.…”

The Intricate Role of CXCR4 in Cancer

“…Also, in patients with known metastatic RCC, CXCR4 was shown to be expressed on circulating pan-cytokeratin-positive RCC cells (Reckamp et al, 2009). Several studies in preclinical models also confirmed that the CXCR4/CXCL12 axis regulates invasiveness, angiogenesis, and organ-specific metastasis of RCC (D’Alterio et al, 2010; Gahan et al, 2012; Wang et al, 2012, 2009). CXCR4 expression in RCC is correlated with metastatic potential in orthotopic mouse models of human RCC xenografts (Pan et al, 2006).…”

CXCR7/CXCR4 Heterodimer Constitutively Recruits β-Arrestin to Enhance Cell Migration

“…CXCR4 and CXCR7 expression levels were also linked to early and metastatic recurrence in non-small cell lung cancer (63). High CXCR7 expression was inversely correlated with 5-year disease-free survival of patients with non-small cell lung cancer and renal cancer (63,64). Interestingly, targeted overexpression of CXCL11/ITAC in tumor sites displayed antitumor activity in a murine cancer model, and ITAC also served as a potent antagonist of transendothelial migration of CXCR4-and CXCR7-positive human tumor cells (25,65).…”