title: Activin A circulating levels in patients with bone metastasis from breast or prostate cancer.
abstract: Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM- patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM- patients (BC: AUC = 0.71 +/- 0.09, P = 0.03; PC: AUC = 0.73 +/- 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease.
authors.affiliation: Laboratory of Experimental Chemotherapy, Department of Surgery and Oncology, Policlinico Universitario P Giaccone, Via del Vespro 129, 90127, Palermo, Italy. gleto@unipa.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: Leto
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Badalamenti
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Tumminello
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Carla
authors.initials: C
authors.lastname: Flandina
authors.forename: Marilena
authors.initials: M
authors.lastname: Crescimanno
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Rini
mesh_terms: D028341:Activins / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C422405:activin A; D028341:Activins