title: Identification of a novel biomarker signature associated with risk for bone metastasis in patients with renal cell carcinoma.
abstract: When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1alpha, uPA , and PA I-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions.
authors.affiliation: Inserm, UMRS 940, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Paule
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Deslandes
authors.forename: St Phane E
authors.initials: SP
authors.lastname: Le Mouel
authors.forename: Laurence
authors.initials: L
authors.lastname: Bastien
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Podgorniak
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.forename: Suzanne
authors.initials: S
authors.lastname: Menashi
authors.forename: Fabien
authors.initials: F
authors.lastname: Calvo
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000302:isolation & purification; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor