分化型甲状腺癌肺转移危险因素研究

Risk factors for lung metastasis of differentiated thyroid cancer Chen Bowen

目的探讨分化型甲状腺癌(DTC)肺转移危险因素,预测肺转移的发生及早期诊断肺转移。方法回顾性分析空军军医大学第一附属医院2013年4月至2023年5月间接受^(131)I治疗的442例DTC患者[男145例、女297例,年龄(41.6±13.1)岁],根据病理或临床、影像及实验室检查结果将患者分为肺转移组(124例)和非肺转移组(318例)。采用随机抽样法将患者按7∶3分为训练集(n=309)和验证集(n=133)。采用χ^(2)检验、Mann-WhitneyU检验比较2组患者的临床资料,采用多因素logistic回归分析影响肺转移的因素,采用ROC曲线评价模型预测能力。结果2组患者在性别、原发肿瘤类型、多灶性、甲状腺外组织侵犯、手术次数、^(131)I治疗前甲状腺球蛋白(Tg)值、肿瘤最大径、淋巴细胞绝对值、中性粒细胞绝对值、B-Raf原癌基因丝/苏氨酸蛋白激酶(BRAF)V600E突变方面差异有统计学意义(χ^(2)值:7.72~107.77,z值:-6.50~-2.44,均P<0.05)。多因素logistic回归分析示多灶性[比值比(odds ratio,OR)=5.646,95%CI:1.763~18.089,P=0.004]、BRAF^(V600E)突变(OR=0.184,95%CI:0.062~0.543,P=0.002)、^(131)I治疗前Tg值(OR=1.015,95%CI:1.004~1.025,P=0.005)、淋巴细胞绝对值(OR=0.395,95%CI:0.166~0.940,P=0.036)及肿瘤最大径(OR=1.932,95%CI:1.207~3.093,P=0.006)为影响肺转移的独立因素。列线图预测模型在训练集和验证集的AUC分别为0.899和0.889。结论原发肿瘤越大、多灶、BRAF^(V600E)基因未突变、^(131)I治疗前高Tg值、淋巴细胞绝对值偏低可能被视为DTC患者肺转移的危险因素。

ObjectiveTo investigate the risk factors for lung metastasis from differentiated thyroid cancer(DTC),predict the occurrence of lung metastasis,and diagnose lung metastasis early.MethodsFrom April 2013 to May 2023,442 DTC patients(145 males,297 females;age(41.6±13.1)years)who received^(131)I treatment in the First Affiliated Hospital of the Air Force Medical University were retrospectively analyzed.All patients were divided into lung metastasis group(n=124)and non-lung metastasis group(n=318)according to pathology or clinical,imaging and laboratory test results.Patients were randomly divided into training set(n=309)and validation set(n=133)at the ratio of 7∶3.The differences of clinical data between the two groups were compared byχ^(2)test and Mann-Whitney U test.Factors affecting lung metastasis were analyzed by multivariate logistic regression analysis.ROC curve analysis was used to evaluate the predictive ability of the model.ResultsThe differences of sex,primary tumor type,multifocal,extra thyroid tissue invasion,number of operations,thyroglobulin(Tg)level before^(131)I treatment,maximum diameter of primary lesion,lymphocyte absolute value,neutrophil absolute value and B-Raf proto-oncogene,serine/threonine kinase(BRAF)V600E mutation between the two groups were statistically significant(χ^(2)values:7.72-107.77,z values:from-6.50 to-2.44,all P<0.05).Multivariate logistic regression analysis showed that multifocal(odds ratio(OR)=5.646,95%CI:1.763-18.089,P=0.004),BRAF V600E mutation(OR=0.184,95%CI:0.062-0.543,P=0.002),Tg level before^(131)I treatment(OR=1.015,95%CI:1.004-1.025,P=0.005),lymphocyte absolute value(OR=0.395,95%CI:0.166-0.940,P=0.036)and maximum diameter of primary lesion(OR=1.932,95%CI:1.207-3.093,P=0.006)were independent factors affecting lung metastasis.The AUCs of the training set and validation set obtained by the nomogram prognostic model were 0.899 and 0.889,respectively.ConclusionLarge primary tumor,multiple focus,non-mutated BRAF V600E gene,high Tg level before^(131)I treatment and low lymphocyte absolute value may be considered as risk factors for lung metastasis of DTC.