CD31, EDNRB and TSPAN7 are promising prognostic markers in clear-cell renal cell carcinoma revealed by genome-wide expression analyses of primary tumors and metastases†
Corresponding Author
Daniela Wuttig
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Tel.: +49(0)6221-565964, Fax: +49(0)6221 565382
Cancer Genome Research, Division of Molecular Genetics, German Cancer Research Center and National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, GermanySearch for more papers by this authorStefan Zastrow
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorSusanne Füssel
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorMarieta I. Toma
Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorMatthias Meinhardt
Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorKristin Kalman
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorKerstin Junker
Department of Urology, Friedrich-Schiller-University, Jena, Germany
Search for more papers by this authorJimsgene Sanjmyatav
Department of Urology, Friedrich-Schiller-University, Jena, Germany
Search for more papers by this authorKerstin Boll
Department of Diagnostics and New Technologies, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Search for more papers by this authorJörg Hackermüller
Department of Diagnostics and New Technologies, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Young Investigators Group Bioinformatics and Transcriptomics, Department Proteomics, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany
Search for more papers by this authorAxel Rolle
Department of Thoracic and Vascular Surgery, Coswig Specialized Hospital, Center for Pneumology, Thoracic and Vascular Surgery, Coswig, Germany
Search for more papers by this authorMarc-Oliver Grimm
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorManfred P. Wirth
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorCorresponding Author
Daniela Wuttig
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Tel.: +49(0)6221-565964, Fax: +49(0)6221 565382
Cancer Genome Research, Division of Molecular Genetics, German Cancer Research Center and National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, GermanySearch for more papers by this authorStefan Zastrow
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorSusanne Füssel
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorMarieta I. Toma
Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorMatthias Meinhardt
Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorKristin Kalman
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorKerstin Junker
Department of Urology, Friedrich-Schiller-University, Jena, Germany
Search for more papers by this authorJimsgene Sanjmyatav
Department of Urology, Friedrich-Schiller-University, Jena, Germany
Search for more papers by this authorKerstin Boll
Department of Diagnostics and New Technologies, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Search for more papers by this authorJörg Hackermüller
Department of Diagnostics and New Technologies, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Young Investigators Group Bioinformatics and Transcriptomics, Department Proteomics, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany
Search for more papers by this authorAxel Rolle
Department of Thoracic and Vascular Surgery, Coswig Specialized Hospital, Center for Pneumology, Thoracic and Vascular Surgery, Coswig, Germany
Search for more papers by this authorMarc-Oliver Grimm
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorManfred P. Wirth
Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
Search for more papers by this authorGene lists are available at http://urologie.uniklinikum-dresden.de/ba_labor_research_download.htm
Abstract
Currently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease-free survival (DFS) of patients with clear-cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS — eight synchronously, nine metachronously and seven not metastasized tumors — were determined by genome-wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty-six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS-associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31, EDNRB and TSPAN7 at the mRNA level (n = 86), and for TSPAN7 at the protein level (n = 106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7-positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor-specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.
Supporting Information
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