儿童及青少年分化型甲状腺癌临床病理学特征及预后分析

Analysis of clinicopathological characteristics and prognosis of papillary thyroid carcinoma in children and adolescents at different ages

目的探讨儿童及青少年分化型甲状腺癌(DTC)临床病理学特征和预后出现明显差异的年龄截点。方法回顾性分析2011年1月至2020年12月中国医科大学附属第一医院甲状腺外科收治的年龄≤18岁行手术治疗的74例DTC患者的临床病理学资料,男性20例,女性54例,年龄[M(IQR)]16(4)岁(范围:8~18岁)。首先根据年龄影响预后的受试者工作特征曲线确定年龄截点,根据年龄截点将纳入患者分为两组,再通过Cox比例风险回归模型行单因素和多因素分析,验证年龄是否为独立预后因素;随后使用Kaplan-Meier生存曲线绘制不同年龄患者的生存曲线,并通过生物信息学分析各年龄组患者的差异基因及可能影响的信号转导通路。结果受试者工作特征曲线确定的年龄截点为15岁。年龄≤15岁是肿瘤复发的唯一预后因素(HR=4.427,95%CI:1.236~15.859,P=0.022)。年龄≤15岁的DTC患者颈部淋巴结转移数目更多,术后10年无复发生存率更低(50.4%比84.1%,P=0.018)。基因富集分析和差异基因鉴定显示两个年龄组间的差异基因与转化生长因子β信号转导通路以及一些代谢相关信号转导通路相关。结论年龄≤15岁的患者颈部淋巴结转移数目较多,年龄≤15岁是儿童及青少年DTC的唯一不良预后因素。对于年龄较小的DTC患者,应采取更加积极的治疗措施和更加严密的术后管理策略。

Objectives To examine the age cut-off point for poor clinicopathological characteristics and prognosis of differentiated thyroid carcinoma(DTC)in children and adolescents.Methods The clinicopathological features of 74 patients with DTC aged 18 years and younger who underwent surgery in the Department of Thyroid Surgery,the First Hospital of China Medical University from January 2011 to December 2020 were retrospectively analyzed.There were 20 males and 54 females,aged(M(IQR))16(4)years(range:8 to 18 years).Firstly,the cut-off point of age affecting prognosis was determined according to the receiver operator characteristic curve,the patients included in the study were grouped according to the age cut-off,and then the univariate and multivariate analysis for prognostic factors were performed using the Cox risk proportional regression model.The Kaplan-Meier survival curve was used to verify the factors affecting the prognosis and analyzed the possible mechanisms by bioinformatics.Results The cut-off value of age was 15 years.Age≤15 years was the only prognostic factor for recurrence(HR=4.427,95%CI:1.236 to 15.859,P=0.022).The number of metastatic cervical lymph nodes was higher in patients aged≤15 years,and the 10-year recurrence-free survival rate was much lower than in patients aged>15 years(50.4%vs.84.1%,P=0.018).Gene enrichment analysis and differential gene identification showed that differential genes between≤15 years old group and>15 years old group were closely related to the transforming growth factor-βsignaling pathway and some metabolism-related signaling pathways.Conclusions Age≤15 years is the only prognostic factor for the prognosis of DTC in children and adolescents.Age≤15 years had more cervical lymph node metastases and a worse prognosis.For younger DTC patients,more active treatment and a stricter postoperative management strategy should be adopted.