Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma
Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma
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作者：
Mizutani, Y;Matsubara, H;Miki, T
背景肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand，TRAIL）在淋巴细胞介导的杀伤恶性肿瘤细胞的过程中起重要作用。骨保护素（OPG）是TRAIL的可溶性诱饵受体，并且循环OPG已经涉及保护细胞免受TRAIL介导的凋亡。因此，OPG可以保护肿瘤细胞免受淋巴细胞介导的细胞毒性，从而促进肿瘤进展。在目前的研究中，作者调查了膀胱癌患者的这一假设。采用酶联免疫吸附法测定185例膀胱癌患者血清OPG水平。然后评估这些水平与各种疾病特征和结局指标的潜在相关性。膀胱癌患者的平均血清OPG浓度约为健康个体平均浓度的3倍，在膀胱癌患者中，发现较高的肿瘤分期和分级与血清OPG水平升高相关。在浅表性膀胱癌患者亚群中，经过5年的随访，与血清OPG水平较高的患者相比，血清OPG水平较低的患者术后无肿瘤间隔时间更长。此外，在肌层浸润性膀胱癌患者中，血清OPG水平低的患者的5年疾病特异性生存率高于血清OPG水平高的患者。据作者所知，目前的研究首次证明血清OPG浓度与肿瘤分期和肿瘤分级相关，血清OPG水平升高可预测膀胱癌患者的早期复发。这些结果表明，血清OPG浓度可能有效用作为一个预后参数在这种情况下。
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.