Differential role of CD133 and CXCR4 in renal cell carcinoma.
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.
Department of Oncological Immunology, S Pio da Pietrelcina Hospital Vasto, Italy.
Crescenzo
C
D'Alterio
Luca
L
Cindolo
Luigi
L
Portella
Marianeve
M
Polimeno
Claudia
C
Consales
Anna
A
Riccio
Michele
M
Cioffi
Renato
R
Franco
Paolo
P
Chiodini
Giacomo
G
Cartenì
Vincenzo
V
Mirone
Nicola
N
Longo
Luigi
L
Marra
Sisto
S
Perdonà
Luigi
L
Claudio
Massimo
M
Mascolo
Stefania
S
Staibano
Mario
M
Falsaperla
Marco
M
Puglisi
Guido
G
Martignoni
Vincenzo
V
Ficarra
Giuseppe
G
Castello
Stefania
S
Scala
D000071916:AC133 Antigen; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019718:Receptors, CXCR4