Chemokines involved in tumor promotion and dissemination in patients with renal cell cancer

Article type: Research Article

Authors: Tsaur, Igor^{a; *} | Noack, Anika^a | Waaga-Gasser, Ana Maria^b | Makarevic, Jasmina^a | Schmitt, Lars^a | Kurosch, Martin^a | Huesch, Tanja^a | Wiesner, Christoph^a | Wedel, Steffen^a | Bartsch, Georg^a | Ackermann, Hanns^c | Oppermann, Elsie^d | Lazariotou, Maria^b | Gasser, Martin^b | Haferkamp, Axel^{a; 1} | Blaheta, Roman A.^{a; 1}

Affiliations: [a] Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany | [b] Department of Surgery I, University of Wuerzburg, Wuerzburg, Germany | [c] Institute of Biostatistics, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany | [d] Department of Surgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

Correspondence: [*] Corresponding author: Dr. med. Igor Tsaur, Johann Wolfgang Goethe-University, Department of Urology, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. Tel.: +49 69 6301 5352; Fax: +49 69 6301 81468; E-mail: [email protected].

Note: [1] Contributed equally as senior authors.

Abstract: Background:Chemokines play a critical role in tumor initiation, progression, and metastasis and have been associated with poor prognosis in diverse malignancies. The prognostic impact of chemokines for renal cell cancer (RCC) remains to be defined. Methods:Patients diagnosed with RCC and operated between 07/07 and 05/11 were differentially assessed for expression profiles of a series of chemokines and their receptors by RT-qPCR and Western Blot analysis (tumor and adjacent normal tissue, n=37) and by Luminex for corresponding serum expression levels. Results were statistically correlated with clinicopathologic parameters. Results:Gene expression of CCL2, CCR7, CXCL12, CXCR3, CXCR5 and CX3CL1 chemokines was significantly down-regulated in tumor compared to normal tissue. The gene profile for CCR6 was positively correlated with tumor size and stage. A positive linear correlation was found between CXCL12 and tumor stage as well as between CX3CR1 and C-reactive protein. In contrast to clear cell RCCs those of a chromophobe type showed a significantly down-regulated gene expression for CCR6, CCL20, and CXCL12. The CXCR7 serum level was significantly increased in patients with tumor-related mortality during postoperative follow-up. Conclusions:Chemokines may serve as novel diagnostic and prognostic biomarkers for RCC. Studies on larger collectives are required for further assessment of potential clinical application.

Keywords: Chemokine, ligand, renal cell cancer, biomarker, diagnosis

DOI: 10.3233/CBM-2012-0247

Journal: Cancer Biomarkers, vol. 10, no. 5, pp. 195-204, 2012