基于新一代基因测序技术的甲状腺乳头状癌基因突变与临床特点分析

发布时间：2018-09-04 15:06

【摘要】：甲状腺乳头状癌(Papillary thyroid carcinoma PTC)是甲状腺癌中最常见的类型,五年生存率可达97.9%[1]。然而在这类良好分化的肿瘤当中仍有部分患者预后差、总体生存率低。鉴于甲状腺乳头状癌发病率的不断上升,亚临床结节的检出增多,寻找一种可靠的复发风险评估方法甄别高危人群指导临床决策显得极为重要。BRAF基因突变是甲状腺乳头状癌中发生频率最高的基因事件,多项研究表明BRAFV600E与甲状腺乳头状癌的淋巴结转移、包膜外侵犯、晚期病理分级相关。随着对甲状腺癌分子标记物的深入研究,其他分子标记物在甲状腺癌的预后、复发风险评估中的作用也受到更多关注,如BEAF与PIK3CA、AKT1、TERT启动子突变、TP53突变的联合可能作为甲状腺乳头状癌不良结局的特异性指标。本研究应用新一代基因测序技术,使用46个肿瘤致病通路基因芯片对52例甲状腺乳头状癌患者进行46个肿瘤致病通路基因热点位置测序,经数据处理、软件分析等流程检测出29例BRAF突变、6例PIK3CA突变、2例TP53突变、2例PTEN基因缺失、3例APC突变、3例STK11突变、其中6例BRAF突变样本合并有其他基因事件。收集患者性别、年龄、肿瘤直径、是否伴有淋巴结转移、是否伴有桥本氏甲状腺炎、多灶性、TNM分期、复发风险分层各项指标,分析BRAF突变、PIK3CA突变与各项临床指标间的相关性。结果显示BRAF突变与性别相关(P0.05)与年龄、肿瘤直径、是否伴有淋巴结转移、是否伴有桥本氏甲状腺炎、多灶性、TNM分期、复发风险分层各项指标之间无关联。多因素分析显示性别不是BRAF突变的独立风险因素。卡方趋势性检验显示PIK3CA突变和复发风险分层相关(P0.001),随复发风险分层级别增加突变频率增高。在高复发风险组患者中观察到6例患者(6/8)有两个或两个以上基因异常,推测多个基因事件的联合作用可能和甲状腺乳头状癌的侵袭性增加、复发风险增高相关。
[Abstract]:Thyroid papillary carcinoma (Papillary thyroid carcinoma PTC) is the most common type of thyroid carcinoma with a 5-year survival rate of 97. 9% [1]. However, some of these well-differentiated tumors still have poor prognosis and low overall survival rate. In view of the increasing incidence of papillary thyroid carcinoma and the increased detection of subclinical nodules, It is very important to find a reliable method to evaluate the risk of recurrence. BRAF gene mutation is the most frequently occurring gene event in papillary thyroid carcinoma. A number of studies have shown that BRAFV600E is associated with lymph node metastasis, extracapsular invasion, and late pathological grade of papillary thyroid carcinoma. With the further study of thyroid cancer molecular markers, the role of other molecular markers in the prognosis and recurrence risk assessment of thyroid cancer has also received more attention. For example, the combination of BEAF and PIK3CA,AKT1,TERT promoter mutation TP53 may be a specific marker for the adverse outcome of papillary thyroid carcinoma. In this study, 46 gene hotspots of tumor pathogenicity pathway were sequenced in 52 patients with papillary thyroid carcinoma by using 46 tumor pathogenetic pathway gene chips by using a new generation of gene sequencing technique, and the data were processed. 29 cases of BRAF mutation 6 cases of PIK3CA mutation 2 cases of TP53 mutation 2 cases of PTEN gene deletion 3 cases of APC mutation 3 cases of STK11 mutation were detected by software analysis. Among them 6 cases of BRAF mutation sample combined with other gene events. The patients' sex, age, tumor diameter, lymph node metastasis, Hashimoto's thyroiditis, multi-focal TNM staging and risk stratification of recurrence were collected. The correlation between BRAF mutation and clinical parameters was analyzed. The results showed that there was no correlation between BRAF mutation and sex (P0.05), age, tumor diameter, lymph node metastasis, Hashimoto's thyroiditis, multi-focal stage and recurrence risk stratification. Multivariate analysis showed that gender was not an independent risk factor for BRAF mutation. Chi square trend test showed that PIK3CA mutation was correlated with recurrence risk stratification (P0. 001), and the mutation frequency increased with the increase of recurrence risk stratification level. Two or more gene abnormalities were observed in 6 patients (6 / 8) with high risk of recurrence, suggesting that the combined effect of multiple gene events may be associated with increased invasive and recurrence risk of papillary thyroid carcinoma.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R736.1

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