Johansen Julia S, Brasso Klaus, Iversen Peter, Teisner Børge, Garnero Patrick, Price Paul A, Christensen Ib Jarle
Department of Rheumatology, Herlev Hospital, , Denmark.
Clin Cancer Res. 2007 Jun 1;13(11):3244-9. doi: 10.1158/1078-0432.CCR-06-2616.
Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment.
Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling).
After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P < 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P < 0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P < 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001), BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of early death.
Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.
转移性前列腺癌（PC）患者在诊断时骨转换生化标志物和YKL-40血清水平升高与预后不良相关。在本研究中，我们评估了这些生物标志物在激素治疗期间监测患者的价值。
在一项对106例转移性PC患者进行的纵向研究中，采用酶联免疫吸附测定法（ELISA）检测血清I型前胶原N端前肽（PINP）、骨特异性碱性磷酸酶（BAP）、CTX-I和YKL-40，这些患者接受全雄激素阻断或胃肠外雌激素治疗。每隔3个月采集血清样本。中位观察时间为4.9年（范围3.6 - 6.2年）。共有78例患者死亡（64例在最后一次采血后7个月内死亡）。
治疗6个月后，与基线值相比，血清PINP、BAP和YKL-40下降（P < 0.0001），但血清CTX-I未下降。单因素Cox分析显示，6个月时的血清PINP[对数转换并作为连续变量处理；风险比（HR），2.2；P < 0.0001]、血清BAP（HR，1.8；P < 0.0001）和血清CTX-I（HR，2.4；P < 0.0001）与生存相关，但血清YKL-40（HR，1.4；P = 0.16）与生存无关。多因素Cox分析纳入治疗开始6个月后的生物标志物，结果显示索洛韦评分（HR，3.9；P = 0.013）、世界卫生组织肿瘤分级（HR，3.9；P = 0.004）和血清PINP（HR，2.2；P < 0.0001）是生存的独立预后变量。在单因素Cox回归分析中将治疗期间的生物标志物作为时间依赖性协变量进行评分，结果显示血清PINP升高（HR，2.0；P < 0.0001）、BAP升高（HR，2.1；P < 0.0001）和YKL-40升高（HR，2.1；P < 0.0001）是早期死亡的预测因素。
在激素治疗期间对转移性PC患者的血清PINP、BAP、CTX-I和YKL-40进行连续监测可提供预后信息。
