作者：王秋桐1，吴爽1，杨艳梅1，王明2，陈玲1，安跃震3，姜俊杰4，王瀚森5，赵瑞6

单位：

1.061001河北省沧州市，沧州医学高等专科学校　2.061001河北省沧州市中心医院肿瘤科3. 061001河北省沧州市中心医院检验科　4. 061001河北省沧州市中心医院甲乳外一科5.061000 河北省沧州市妇幼保健院病理科　6.100020北京市，首都医科大学附属北京朝阳医院药事部

Units：

1.Cangzhou Medical College?Hebei?China, Cangzhou 061001, China 2.Department of Oncology, Cangzhou Central Hospital, Cangzhou 061001, China3.Department of Laboratory, Cangzhou Central Hospital, Cangzhou 061001, China4.Department of Thyroid and Breast Branch, Cangzhou Central Hospital, Cangzhou 061001, China5.Department of Pathology, Cangzhou Women and Children's Health, Cangzhou 061000, China6.Department of Pharmacy, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, China

关键词：

癌，非小细胞肺；凝血功能指标；生物标记，肿瘤；静脉血栓栓塞；远端转移；诊断

Keywords：

Carcinoma, non-small-cell lung; Coagulation function index; Biomarkers, tumor; Venousthromboembolism; Distant metastasis; Diagnosis

CLC：

R 730.26

DOI：

10.12114/j.issn.1008-5971.2022.00.238

Funds：

沧州市重点研发计划指导项目（213106072）

摘要：

目的　分析非小细胞肺癌（NSCLC）患者凝血功能指标与肿瘤标志物的相关性，并评估其对NSCLC患者合并静脉血栓栓塞症（VTE）、远端转移的诊断价值。方法　回顾性选取2019年1月至2020年1月沧州市中心医院肿瘤科收治的NSCLC患者145例为研究对象。根据合并VTE情况，将患者分为VTE组（25例）和非VTE组（120例）；根据合并远端转移情况，将患者分为远端转移组（12例）和非远端转移组（133例）。收集患者临床资料；凝血功能指标〔纤维蛋白原（FIB）、D-二聚体（D-D）〕与肿瘤标志物〔癌胚抗原（CEA）、神经元烯醇化酶（NSE）、糖类抗原125（CA125）、鳞状上皮细胞癌抗原（SCC-Ag）、细胞角蛋白19片段抗原21-1（CYFRA21-1）〕的相关性分析采用Spearman秩相关分析；NSCLC患者合并VTE、远端转移的影响因素分析采用多因素Logistic回归分析；采用ROC曲线评估凝血功能指标、肿瘤标志物及其联合对NSCLC患者合并VTE、远端转移的诊断价值。结果　NSCLC患者FIB与CA125、CYFRA21-1呈正相关，D-D与NSE、CA125、CYFRA21-1呈正相关（P ＜0.05）。VTE组FIB、D-D、CEA、CA125、CYFRA21-1高于非VTE组（P ＜0.05）。多因素Logistic回归分析结果显示，FIB、D-D、CEA、CA125、CYFAR21-1是NSCLC患者合并VTE的独立影响因素（P ＜0.05）。FIB、FIB+D-D、FIB+CEA、FIB+CA125、FIB+CYFAR21-1、FIB+D-D+CEA、FIB+D-D+CA125、FIB+D-D+CYFAR21-1、FIB+CEA+CA125、FIB+CEA+CYFAR21-1、FIB+CA125+CYFAR21-1、FIB+D-D+CEA+CA125、FIB+D-D+CEA+CYFAR21-1、FIB+DD+CA125+CYFAR21-1、FIB+CEA+CA125+CYFAR21-1、FIB+D-D+CEA+CA125+CYFAR21-1诊断NSCLC患者合并VTE的AUC均＞0.9，且FIB+D-D+CEA+CA125诊断NSCLC患者合并VTE的AUC为0.991。远端转移组东部肿瘤协作组（ECOG）体能状态评分、VTE发生率、FIB、D-D、CA125、CYFRA21-1高于非远端转移组（P ＜0.05）。多因素Logistic回归分析结果显示，ECOG体能状态评分、D-D是NSCLC患者合并远端转移的独立影响因素（P ＜0.05）。ROC曲线分析结果显示，ECOG体能状态评分+D-D诊断NSCLC患者合并远端转移的AUC为0.921。结论　NSCLC患者FIB与CA125、CYFRA21-1呈正相关，D-D与NSE、CA125、CYFRA21-1呈正相关；FIB、D-D、CEA、CA125、CYFAR21-1升高是NSCLC患者合并VTE的独立危险因素，且FIB+D-D+CEA+CA125对NSCLC患者合并VTE的诊断价值较高；ECOG体能状态评分、D-D升高是NSCLC患者合并远端转移的独立危险因素，且二者联合对NSCLC患者合并远端转移有较高的诊断价值。

Abstract：

Objective　To analyze the correlation between coagulation function indexes and tumor markers in patientswith non-small cell lung cancer (NSCLC) , and evaluate their diagnostic value for venous thromboembolism (VTE) and distantmetastasis in patients with NSCLC. Methods　A total of 145 patients with NSCLC who were admitted to the Department ofOncology, Cangzhou Central Hospital from January 2019 to January 2020 were retrospectively selected as the research subjects.According to the combined VTE, the patients were divided into VTE group (25 cases) and non-VTE group (120 cases) . Thepatients were divided into distant metastasis group (12 cases) and non-distant metastasis group (133 cases) according to thecomplicated distant metastasis. Clinical data of patients were collected. Spearman rank correlation analysis was used to analyzethe correlation between coagulation function indicators [fibrinogen (FIB) , D-dimer (D-D) ] and tumor markers [carcinoembryonicantigen (CEA) , neuron-specific enolase (NSE) , carbohydrate antigen 125 (CA125) , squamous cell carcinoma antigen (SCC-Ag) ,cytokeratin 19 fragment antigen21-1 (CYFRA21-1) ] . Multivariate Logistic regression analysis was used to analyze the influencingfactors of VTE and distant metastasis in patients with NSCLC. ROC curve was used to evaluate the diagnostic value of coagulationfunction indicators, tumor markers and their combination for VTE and distal metastasis in patients with NSCLC. Results　FIBwas positively correlated with CA125 and CYFRA21-1, and D-D was positively correlated with NSE, CA125 and CYFRA21-1in patients with NSCLC (P < 0.05) . The FIB, D-D, CEA, CA125, and CYFRA21-1 in the VTE group were higher than thosein the non-VTE group (P < 0.05) . The results of multivariate Logistic regression analysis showed that FIB, D-D, CEA, CA125,and CYFAR21-1 were independent influencing factors of VTE in patients with NSCLC (P < 0.05) . The AUCs of FIB, FIB+D-D,FIB+CEA, FIB+CA125, FIB+CYFAR21-1, FIB+D-D+CEA, FIB+D-D+CA125, FIB+D-D+CYFAR21-1, FIB+CEA+CA125,FIB+CEA+CYFAR21-1, FIB+CA125+CYFAR21-1, FIB+D-D+CEA+CA125, FIB+D-D+CEA+CYFAR21-1, FIB+DD+CA125+CYFAR21-1, FIB+CEA+CA125+CYFAR21-1 and FIB+D-D+CEA+CA125+CYFAR21-1 in the diagnosis of VTE inpatients with NSCLC were all > 0.9, and the AUC of FIB+D-D+CEA+CA125 in the diagnosis of VTE in patients with NSCLC was0.991. The Eastern Cooperative Oncology Group (ECOG) performance status score, combined VTE rate, FIB, D-D, CA125, andCYFRA21-1 in the distant metastasis group were higher than those in the non-distant metastasis group (P < 0.05) . MultivariateLogistic regression analysis showed that ECOG performance status score and D-D were independent influencing factors of distantmetastasis in patients with NSCLC (P < 0.05) . The results of ROC curve analysis showed that the AUC of ECOG performance statusscore+D-D in the diagnosis of distant metastasis in patients with NSCLC was 0.921. Conclusion　In NSCLC patients, FIB ispositively correlated with CA125 and CYFRA21-1, and D-D is positively correlated with NSE, CA125 and CYFRA21-1. Elevatedlevels of FIB, D-D, CEA, CA125, and CYFAR21-1 are independent risk factors for VTE in patients with NSCLC, and FIB+DD+CEA+CA125 has higher diagnostic value for VTE in patients with NSCLC. Elevated ECOG performance status score and D-Dare independent risk factors for distant metastasis in patients with NSCLC, and the combination of the two has high diagnostic valuefor distant metastasis in patients with NSCLC.

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