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甲状腺乳头状癌基因突变与其侵袭性相关性研究
作者姓名:张冉  杨洁  冯恩梓  袁晓凤  王清
作者单位:昆明医科大学第三附属医院头颈外科,云南 昆明 650118
基金项目:云南省医学学科带头人培养计划项目(D-2018004)
摘    要:  目的  收集就诊于昆明医科大学第三附属医院的甲状腺乳头状癌(papillary thyroid carcinoma,PTC)患者的临床、病理及基因资料并整理分析,探究PTC基因突变与其侵袭性的相关性,并探讨BRAF V600E单基因突变与中央区淋巴结隐匿性转移的相关性,以期细化PTC的精准治疗。  方法  选择2018年4月至2022年4月就诊于昆明医科大学第三附属医院符合入组标准且同意入组的PTC患者,收集入组患者临床病理及基因资料并整理分析:(1)各基因突变作观察组、野生型作对照,对比各基因型突变与野生型的差异;(2)多基因突变作观察组,单基因突变作对照,对比多基因突变与单基因突变的差异; (3)cN0患者中:BRAF V600E单基因突变作观察组,无基因突变作对照,分析BRAF V600E突变与中央区淋巴结隐匿性转移的相关性。  结果  (1)BRAFV600E突变:中央区淋巴结转移(Central Lymph Node Metastasis CLNM)、N1占比大,转移淋巴结数目多,TPO-Ab降低(P < 0.05);TERT突变:高龄、男性、侧颈淋巴结转移占比大,侧颈淋巴结转移数目多,T分期晚(P < 0.05);RET突变:侧颈淋巴结转移占比大、侧颈转移淋巴结数目多,T分期晚(P < 0.05),NTRK3与ETV6均融合突变,结果一致:突变组侵犯甲状腺包膜占比大(P < 0.05);RAS突变:Tg-Ab水平低(P < 0.05);TP53,CCDC6:突变组与野生型组未见明显差异(P≥0.05);(2)多基因突变组侵犯包膜、侧颈淋巴结转移占比大、侧颈转移淋巴结数量多,M分期晚(P < 0.05);3.cN0患者中:BRAF V600E单基因突变组CLNM占比大,中央区转移淋巴结数目较多(P < 0.05)。  结论  (1)PTC中,BRAF V600E突变与中央区淋巴结转移相关;(2)多基因突变较单基因突变表现出更强的侧颈淋巴结及远处转移能力;(3)cN0 PTC患者中,BRAF V600E单基因突变与隐匿性中央区淋巴结转移有关。

关 键 词:甲状腺乳头状癌    侵袭性    包膜侵犯    淋巴结转移    基因突变
收稿时间:2022-12-12

Correlation between Gene Mutation and Invasiveness in Papillary Thyroid Carcinoma
Affiliation:Dept. of Head and Neck Surgery,The 3rd Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650118,China
Abstract:  Objective  In this study, the clinical, pathological and genetic data of PTC patients in The Third Affiliated Hospital of Kunming Medical University were collected, sorted out and statistically analyzed to explore the correlation between PTC gene mutations and the aggressiveness of PTC. Besides, the correlation between BRAF V600E mutation and the occult metastasis of central lymph nodes in PTC was discussed, so as to refine the precise treatment of PTC.   Methods  PTC patients who met the inclusion criteria and agreed to be enrolled in the Third Affiliated Hospital of Kunming Medical University from April 2018 to April 2022 were selected. The genetic, pathological and clinical data were collected and analyzed. (1) Each gene mutation group was used as the observation group and the wild-type was used as the control group to compare the difference between each gene mutation and wild type. (2) Multiple gene mutations were used as observation group and single gene mutations were used as control group to compare the difference between multiple gene mutation and single gene mutation. (3) In cN0 patients: BRAF V600E single gene mutation was used as observation group and without gene mutation was used as control group to analyse the correlation between the BRAF V600E and he occult metastasis of central lymph nodes in PTC .   Results  (1) BRAF V600E mutation: CLNM and N1 accounted for a large proportion and the number of central lymph node metastasis was high , TPO-Ab reduced (P < 0.05); TERT mutant: Elderly, male, lateral neck lymph node metastasis accounted for a large proportion and the number of lateral neck lymph node metastasis was high, T stage was later (P < 0.05). RET mutant: Lateral neck lymph node metastasis accounted for a large proportion and the number of lateral neck lymph node metastasis was high, T stage was late (P < 0.05). NTRK3 and ETV6 were fused together, and the results were consistent: in the mutant group, the invasion of thyroid capsule accounted for more (P < 0.05). RAS mutation: Tg-Ab was reduced (P < 0.05); TP53、CCDC6: There was no significant difference between the mutant group and the wild-type group (P ≥ 0.05). (2) Thyroid capsule invasion, lateral neck lymphatic metastasis accounted for a large proportion and more metastatic lymph nodes in the lateral neck, M stage was later in Multiple gene mutations group (P < 0.05); (3) In patients with cN0: CLNM accounted for a large proportion and the number of lateral neck lymph node metastasis was high in BRAF V600E single mutation group (P < 0.05).  Conclusions  (1) BRAF V600E mutation is associated with CLNM in PTC. (2) Multi-gene mutation shows stronger lateral neck lymph node and distant metastasis ability than single gene mutation. (3) BRAF V600E mutation is associated with the occult metastasis of the central lymph node in cN0 PTC patients.
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