血清N-MID在原发性肺癌患者骨转移辅助诊断和疗效监测中的应用分析

背景与目的：目前临床上用于原发性肺癌患者骨转移辅助诊断的血清学标志物相对缺乏，探讨血清中骨钙素（osteocalcin，OC）N端中分子片段（N-terminal mid-fragment，N-MID）的表达水平在肺癌患者骨转移辅助诊断和疗效监测中的作用。方法：选取2017年3月—2018年2月在复旦大学附属肿瘤医院诊断为原发性肺癌的231例患者作为实验组，其中包括97例肺癌合并骨转移的患者和134例未骨转移的肺癌患者，选取69名同期健康体检者作为健康对照组。利用logistic多因素回归模型分析血清N-MID、癌胚抗原（carcinoembryonic antigen，CEA）、神经元特异性烯醇化酶（neuron-specific enolase，NSE）、细胞角蛋白19片段（cytokeratin 19 fragment，CYFRA21-1）、碱性磷酸酶（alkaline phosphatase，ALP）等在肺癌骨转移中的相关性。结果：治疗前骨转移组血清N-MID水平明显高于无骨转移组和健康对照组（P均 ＜ 0.001）。Logistic多因素分析显示，血清N-MID（OR=9.265）和NSE水平（OR=2.688）是肺癌患者发生骨转移的危险因素。通过受试者工作特征（receiver operating characteristic，ROC）曲线确定血清N-MID的临界值为14.96 ng/mL，并将实验组分为N-MID ＞ 14.96 ng/mL组和N-MID≤14.96 ng/mL组。治疗前，血清N-MID ＞ 14.96 ng/mL组肺癌患者的无进展生存期（progression-free survival，PFS）明显低于N-MID≤14.96 ng/mL组患者（HR=2.040）。在肺癌合并骨转移患者中，治疗前后血清N-MID水平降低提示疾病缓解（P ＜ 0.001）。结论：血清N-MID水平与肺癌合并骨转移存在相关性，检测治疗前后的血清N-MID浓度可用于肺癌患者骨转移的辅助诊断和疗效监测。

The application of serum N-MID in auxiliary diagnosis and therapeutic effect monitoring of bone metastasis in patients with primary lung cancer

Background and purpose:?There is a lack of serum markers for the diagnosis of bone metastasis in patients with primary lung cancer currently. This study aimed to explore the expression level of serum N-terminal mid-fragment (N-MID) of osteocalcin (OC) and its functions in the diagnosis and therapy monitoring of bone metastasis in patients with lung cancer. Methods: A total of 231 patients with clinically classified primary lung cancer in Fudan University Shanghai Cancer Centre from March 2017 to February 2018 were enrolled as the experimental group, including 97 patients with bone metastasis and 134 without bone metastasis. Sixty-nine healthy adults without cancer were included in the same period as the healthy control group. Serum levels of N-MID, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1) and alkaline phosphatase (ALP) were measured. The correlation with clinical characteristics of bone metastasis in lung cancer was analyzed by using multivariate logistic regression analysis. Results: Expression levels of N-MID before treatment were significantly higher in the bone metastasis group than in the group without bone metastasis (P ＜ 0.001) and healthy control group (P ＜ 0.001). According to the results of multivariate logistic regression analysis, the serum levels of N-MID (OR=9.265) and NSE (OR=2.688) were risk factors of bone metastasis in lung cancer patients. The cut-off level of serum N-MID was determined as 14.96ng/mL by the receiver operatingcharacteristic (ROC) curve, and the experimental group was divided into two subgroups. The progression-free survival (PFS) of lung cancer patients whose serum N-MID levels were higher than 14.96ng/mL before treatment was significantly lower than that of patients with N-MID level lower than 14.96ng/mL (HR=2.040). In lung cancer patients with bone metastasis, the decrease of serum N-MID level after treatment indicated remission (P ＜ 0.001). Conclusion: The serum level of N-MID is closely correlated to the bone metastasis in lung cancer. The detection of serum N-MID before and after treatment can be applied in both auxiliary diagnosis and monitoring therapeutic effect in lung cancer patients with bone metastasis.