Differential role of CD133 and CXCR4 in renal cell carcinoma

Abstract

The chemokine receptor CXCR4 and CD133, putative stem cell markers, were previously described in renal cancer (RCC). To evaluate the biological and prognostic role of CD133 and CXCR4 in RCC the expression was evaluated through qPCR and immunoblotting in human renal cancer cell lines (786-O, A498, ACHN, CAKI-1, SN12C, TK10, UO31) and patients biopsies. Renal cancer cells and surgical biopsies expressed functional CXCR4 while CD133 was not detectable. CXCR4 and CD133 expression was then evaluated in 240 renal cancer patients through immunohistochemistry. CXCR4 and CD133 were low in 19.1% and 59.6%; intermediate in 20% and 17.9%; high in 60.8% and 22.5% of the cases, respectively. CXCR4 was overexpressed in tumours (p= 0.02), while CD133 was over expressed in healthy tissues (p= 0.04). Disease free survival Kaplan Meier plots suggest that prognosis is unfavourable for patients whose primary tumours express CXCR4 (p= 0.0199) but nor CD133 (p= 0.151) neither the concomitant CXCR4-CD133 (p=0.848) high expression affected prognosis. Analysis of prognostic factors suggests that age, clinical presentation, AJCC stage and CXCR4 had a significant prognostic value at the univariate analysis. The CXCR4 predictive ability was confirmed at the multivariate analysis while no prognostic role was identified for CD133.Thus concomitant CD133 and CXCR4 evaluation is not worth in RCC patient while the CXCR4 prognostic role encourage CXCR4 antagonists as promising therapeutic option.

Co-expression of CXCR4 and CD133 in gastric neoplastic tissue and their correlation with clinicopathological factors and prognosis in gastric cancer

“…13,14 Distinct immunostaining pattern of CXCR4 in cytomembrane and/or nucleus is associated with high tumor stage of liver carcinoma and metastasis of ranal cancer. 15,16 In the light of this report our results indicate that high expression of CXCR4 may be correlated with symptomatic and advanced stages of disease and suggesting their definitive role in prognosis of the disease.…”

CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis

“…Interestingly, high expression of MMP9 in primary RCC has been demonstrated to be associated with poor prognosis of RCC patients [50]. The properties of CXCR4 þ CSCs also seem to be relevant in RCC patients, since high levels of CXCR4 mRNA or higher content of CXCR4 þ cells were associated with a poor prognosis ( [36,51] and this work). Interestingly, only M0 patients with high CXCR4 mRNA content in their primary tumors, indicating a higher number of CSCs, were more likely to succumb to metastasis, accompanied by a shorter survival time.…”

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

“…For example, chemokine receptor CXCR4 was reported to be 2.01-fold upregulated in the Caki-1 cell line; this was previously reported as a cancer stem cell marker, and CXCR4-positive cells exhibit great resistance to tyrosine kinase inhibitors (27,42,47). In addition, CXCR4 expression has significant prognostic value and therapeutic importance in RCC patients (13). IL-6 expression, meanwhile, was 19.88-fold upregulated in the Caki-1 cell line.…”