title: Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications.
abstract: The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (M0) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS; p=0.0008) or in patients with primary osteoporosis (OP; p=0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS (p=0.0001) or OP (p=0.017). In PCa patients, cathepsin K concentrations did not significantly differ from those measured in sex matched HS or in patients with benign prostatic hyperplasia (BPH). Conversely, cystatin C was more elevated in cancer patients than in controls (p=0.0001) or BPH patients (p=0.0078). Furthermore, in PCa patients, a positive correlation was observed between cystatin C and cathepsin K (r(S)=0.34; p=0.047). No further relationship was highlighted between these molecules and the clinicobiological parameters of BCa or PCa progression including the number of bone lesions. Moreover, ROC curve analysis showed a poor diagnostic performance of cathepsin K and cystatin C in the detection of BM patients. Interestingly, the administration of zoledronic acid (ZA), a bisphosphonate derivative endowed with a potent antiosteoclastic activity, induced in BM patients a marked increase of cathepsin K and cystatin C serum levels compared to baseline values. However, this phenomenon was statistically significant only in the PCa group. In conclusion Cystatin C and cathepsin K may be regarded as possible markers to monitor the therapeutic response to bisphosphonate treatments. Nevertheless, their clinical value as specific gauges of skeletal metastasis remains questionable.
authors.affiliation: Laboratory of Experimental Chemotherapy, Department of Surgery and Oncology, Policlinico Universitario P. Giaccone, Via del Vespro 129, 90127 Palermo, Italy.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Tumminello
authors.forename: Carla
authors.initials: C
authors.lastname: Flandina
authors.forename: Marilena
authors.initials: M
authors.lastname: Crescimanno
authors.forename: Gaetano
authors.initials: G
authors.lastname: Leto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology; D016022:Case-Control Studies; D056657:Cathepsin K; D002403:Cathepsins / Q000097:blood*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D004164:Diphosphonates / Q000494:pharmacology; D018450:Disease Progression; D016903:Drug Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology; D012372:ROC Curve; D000077211:Zoledronic Acid
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K