摘要：
目的 探讨骨代谢标志物总Ⅰ型胶原氨基端延长肽(tP1NP)、β-Ⅰ型胶原羧基端肽(β-CTx)以及骨碱性磷酸酶(BAP)在肺癌骨转移中的诊断、监测及预后价值.方法 采用病例对照研究,选择2014至2015年间于上海交通大学附属第六人民医院就诊的肺癌患者196例,其中肺癌骨转移109例,无骨转移87例,另招募健康志愿者106名作为对照.采集血清,采用化学发光方法定量检测血清中tP1NP、β-CTx和BAP的浓度,并随访患者的预后情况,统计比较肺癌患者骨转移组、无骨转移组以及志愿对照组血清tP1NP、β-CTx和BAP的浓度,并进行受试者工作特征曲线(ROC)分析及Kaplan-Meier生存分析.结果 组间比较发现,肺癌骨转移组血清 tP1NP 浓度100.20(67.07 ~154.60)μg/L 显著高于无骨转移组59.14(47.56~75.94)μg/L(Z=-5.642,P<0.001),肺癌骨转移组血清β-CTx浓度630.3(413.8~948.3)ng/L 高于无骨转移组459.0(356.3~576.9)ng/L(Z=-3.783,P<0.01),肺癌骨转移组血清 BAP 浓度17.77(10.13 ~32.44)μg/L 高于无骨转移组11.87(10.32~15.91)μg/L(Z=-8.923,P<0.01).ROC 曲线分析显示,血清tP1NP、β-CTx 和BAP诊断肺癌骨转移有无的曲线下面积分别为0.874、0.776、0.678;联合tP1NP、β-CTx和BAP诊断肺癌骨转移有无的曲线下面积为0.925(95% CI 0.867~0.963),灵敏度和特异度分别为77.11%、98.11%;血tP1NP和β-CTx浓度水平与骨转移治疗的效果相关,疗效缓解的患者tP1NP浓度水平下降(t=4.607,P<0.05),β-CTx浓度水平亦下降(t=5.355,P<0.05);生存分析提示,tP1NP浓度与肺癌患者预后相关,浓度高预后差[OR=3.287,95% CI(1.118 ~9.661),P<0.05].结论 血清tP1NP、β-CTx和BAP浓度水平可用于肺癌骨转移有无的辅助诊断,指标联合应用诊断效能更高;tP1NP和β-CTx可作为肺癌骨转移疗效监测的辅助指标;血清tP1NP水平可用于肺癌患者预后评估的辅助指标.%Objective To investigate the diagnosis, therapeutic monitoring and prognosis value of the total procollagen type 1 amino-terminal propeptide(tP1NP), beta-C-terminal telopeptide(β-CTx)and bone alkaline phosphatase(BAP)in the bone metastasis of lung cancer.Methods With the case-control study method, the serum levels of tP1NP, β-CTx and BAP in 196 lung cancer patients, including 109 patients with bone metastases,87 patients without bone metastases,and 106 healthy controls at the Shanghai Sixth People′s East Hospital affiliated to Shanghai Jiao Tong University between 2014 and 2015 were quantitatively detected by chemiluminescent immunoassay.Receiver operating characteristic(ROC)curve was calculated to assess the diagnostic value.Survival curve was performed by Kaplan-Meier method. Results The concentration of tP1NP,β-CTx and BAP in the lung cancer patients with bone metastasis were significantly higher than that in the lung cancer patients without bone metastasis(Z=-5.642,P<0.001;Z=-3.783,P<0.01;Z=-8.923,P<0.01).ROC curve analysis showed that the AUC of tP1NP, β-CTx and BAP were 0.874,0.776 and 0.678 respectively(P<0.05).The AUC of the combined three markers was 0.925(95%CI 0.867-0.963),with sensitivity of 77.11% and specificity of 98.11%.The levels of tP1NP and β-CTx were associated with the clinical response.The concentration of tP1NP,β-CTx were significantly decreased in patients achieved remission(t=4.607,P<0.05;t=5.355,P<0.05). Survival analysis showed that higher concentration of tP 1NP was correlated with poor prognosis[OR=3.287, 95%CI(1.118-9.661),P<0.05].Conclusions The levels of tP1NP,β-CTx and BAP cloud be used for the differential diagnosis of bone metastasis of lung cancer,and the combined usage was more effective. tP1NP and β-CTx cloud be used in therapeutic monitoring of lung cancer patients with bone metastasis. Moreover,tP1NP could be used as prognostic biomarker in lung cancer patients.
