不同基因变异型与BRAFV600E突变型甲状腺乳头状癌淋巴结转移特征比较

Comparison of lymph node metastatic characteristics between papillary thyroid carcinomas with different genetic alterations and those with BRAFV600E mutation

摘要:

背景与目的 BRAF^V600E突变是甲状腺乳头状癌（PTC）中最常见的基因变异类型，广泛用于指导手术范围及风险评估。然而，其他基因变异在临床中的分布逐渐增多，其与淋巴结转移的关系尚不明确。已有研究大多将BRAF^V600E突变与BRAF野生型进行对比，未对具体突变类型进行分层分析，可能影响判断的准确率。本研究旨在比较不同常见基因变异类型PTC与BRAF^V600E突变型PTC患者的淋巴结转移特征差异。方法 回顾性纳入2019年1月—2025年1月复旦大学附属肿瘤医院接受手术并完成基因检测的4 795例PTC患者，筛选具有单一基因变异的病例并分组。采用倾向性评分匹配（PSM）控制年龄、性别及T分期等混杂因素后，分别比较各突变组与BRAF^V600E突变组的淋巴结转移数目及N分期。结果 PSM后，CCDC6-RET融合组与NCOA4-RET融合组患者的淋巴结转移数目及N1b分期比例明显高于BRAF^V600E突变组（均P<0.05）。ETV6-NTRK3融合组及RAS突变组在淋巴结转移数目和N分期与BRAF^V600E突变组差异无统计学意义（均P>0.05）。结论 CCDC6-RET及NCOA4-RET融合型PTC患者的淋巴结转移负荷显著高于BRAF^V600E突变型，提示其侵袭性更强；而ETV6-NTRK3融合型和RAS突变型与BRAF^V600E突变型相似。术前基因分型有助于识别高转移风险患者，为制定个体化淋巴结清扫方案提供依据。

Abstract:

Background and Aims The BRAF^V600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC) and is widely used to guide surgical extent and risk stratification. However, other genetic variants are increasingly identified in clinical practice, and their association with lymph node metastasis (LNM) remains unclear. Most existing studies have compared BRAF^V600E-mutated cases with BRAF wild-type cases without stratifying specific mutation types, potentially affecting the accuracy of risk assessment. This study aimed to compare the lymph node metastatic features between PTC patients with different common genetic alterations and those with the BRAF^V600E mutation.Methods A retrospective analysis was conducted on 4 795 PTC patients who underwent surgery and genetic testing at Fudan University Shanghai Cancer Center from January 2019 to January 2025. Patients with a single genetic alteration were included and grouped accordingly. Propensity score matching (PSM) was used to control for confounding factors including age, sex, and T stage. The number of metastatic lymph nodes and N stage were compared between each mutation group and the BRAF^V600E group.Results After PSM, patients in the CCDC6-RET and NCOA4-RET fusion groups had significantly higher numbers of metastatic lymph nodes and N1b stage rates compared to the BRAF^V600E group (all P<0.05). No significant differences were observed between the ETV6-NTRK3 fusion or RAS mutation groups and the BRAF^V600E group in terms of lymph node metastasis or N stage (all P>0.05).Conclusion PTC patients harboring CCDC6-RET or NCOA4-RET fusions exhibit a significantly higher lymph node metastatic burden than those with the BRAF^V600E mutation, suggesting more aggressive behavior. In contrast, ETV6-NTRK3 and RAS-mutated PTCs show similar metastatic profiles to BRAF^V600E-mutated cases. Preoperative genetic profiling may help identify patients at high risk of metastasis and guide individualized lymph node dissection strategies.