Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma.
BACKGROUND
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in the process of lymphocyte-mediated cytotoxicity against malignant cells. Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, and circulating OPG has been implicated in the protection of cells from TRAIL-mediated apoptosis. Thus, OPG may protect tumor cells from lymphocyte-mediated cytotoxicity and, as a result, contribute to tumor progression. In the current study, the authors investigated this hypothesis in patients with bladder carcinoma.


METHODS
Serum OPG levels for 185 patients with bladder carcinoma were determined using an enzyme-linked immunosorbent assay. These levels then were assessed for potential correlations with various disease characteristics and outcome measures.


RESULTS
The mean serum OPG concentration in patients with bladder carcinoma was approximately 3 times greater than the mean concentration in healthy individuals, and among patients with bladder carcinoma, higher tumor stage and grade were found to be associated with increased serum OPG levels. Within the subpopulation of patients with superficial bladder carcinoma, after a follow-up period of 5 years, those who had low serum OPG levels tended to have a longer postoperative tumor-free interval compared with those who had high serum OPG levels. Furthermore, among patients with muscle-invasive bladder carcinoma, the 5-year disease-specific survival rate was greater for those who had low serum OPG levels than for those who had high serum OPG levels.


CONCLUSIONS
To the authors' knowledge, the current study is the first to demonstrate that serum OPG concentration is correlated with both tumor stage and tumor grade and that elevated serum OPG levels are predictive of early recurrence in patients with bladder carcinoma. These findings suggest that serum OPG concentration may have utility as a prognostic parameter in this setting.
Mizutani
Yoichi
Y
Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan. ymizutan@koto.kpu-m.ac.jp
Matsubara
Hiroki
H
Yamamoto
Kosuke
K
Nan Li
Yong
Y
Mikami
Kazuya
K
Okihara
Koji
K
Kawauchi
Akihiro
A
Bonavida
Benjamin
B
Miki
Tsuneharu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000097:blood*; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000556:secondary; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology; D009367:Neoplasm Staging; D053244:Osteoprotegerin; D011182:Postoperative Care; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha