Wang Zhihong, Tang Peng, Hua Surong, Gao Junyi, Zhang Bin, Wan Hua, Wu Qixi, Zhang Jiaxin, Chen Ge
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Department of Breast and Thyroid Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
Onco Targets Ther. 2022 Feb 9;15:147-157. doi: 10.2147/OTT.S339114. eCollection 2022.
To describe the genetic landscape and clinical characteristics of Chinese patients diagnosed with papillary thyroid cancer (PTC) and to determine which high-risk genetic characteristics suggest a likelihood of lymph node metastasis (LNM) and lateral lymph node metastasis (LLNM).
Data from previously untreated patients with PTC collected between May 2018 and December 2020 from 14 hospitals in China were analyzed retrospectively. High-risk pathologic characteristics were defined as T3/T4, N(+), and N1b(+) stages. All patients were tested for 57 genes by second-generation sequencing. The -test, chi-square test, and Fisher's exact test were performed for statistical analysis.
Overall, 395 patients were enrolled in this study. The prevalence of mutation was 78.53%. mutant allele frequency (MAF) >16.93% was associated with a significantly higher risk of LNM, LLNM, and T3 + T4 stage compared with a low-risk group, defined by a MAF <2.54% (odd ratios [ORs] for each risk=3.38, 3.46, and 8.54, respectively), and an intermediate-risk group, defined by a MAF of 2.54% to 16.93% (ORs=2.04, 2.07, and 4.07, respectively). The population with fusion had higher T, N, and N1b stages (ORs for each stage=10.40, 7.60, and 8.77, respectively) compared with a negative population. Similar conclusions about T, N, and N1b stages were observed in relation to multiple driver gene mutations (ORs for each stage=7.48, 2.80, and 7.04, respectively) compared with population without multiple driver mutations. These genetic characteristics may be suggestive of high clinical risk. However, regardless of genetic profiles, patients younger than age 45 years had greater rates of LNM and LLNM.
The main driver gene in this study, , differs significantly between the United States (79% vs 51%) and other countries. The Chinese population in this study that experienced more aggressive tumor biology had a MAF greater than 16.93%, exhibited fusion events, and had multiple driver gene mutations; thus, these traits may be considered high-risk genetic characteristics in PTC that could warrant aggressive treatment in such population.
描述中国乳头状甲状腺癌（PTC）患者的基因图谱和临床特征，并确定哪些高危基因特征提示有淋巴结转移（LNM）和侧方淋巴结转移（LLNM）的可能性。
回顾性分析2018年5月至2020年12月期间从中国14家医院收集的既往未接受治疗的PTC患者的数据。高危病理特征定义为T3/T4、N(+)和N1b(+)分期。所有患者均通过二代测序检测57个基因。采用t检验、卡方检验和Fisher精确检验进行统计分析。
本研究共纳入395例患者。 突变的发生率为78.53%。与低风险组（定义为突变等位基因频率[MAF]<2.54%）和中风险组（定义为MAF为2.54%至16.93%）相比，MAF>16.93%与LNM、LLNM和T3 + T4分期的风险显著更高相关（各风险的比值比[OR]分别为3.38、3.46和8.54）（各风险的OR分别为2.04、2.07和4.07）。与阴性人群相比，发生 融合的人群具有更高的T、N和N1b分期（各分期的OR分别为10.40、7.60和8.77）。与无多个驱动基因突变的人群相比，在多个驱动基因突变方面观察到关于T、N和N1b分期的类似结论（各分期的OR分别为7.48、2.80和7.04）。这些基因特征可能提示高临床风险。然而，无论基因谱如何，45岁以下的患者LNM和LLNM的发生率更高。
本研究中的主要驱动基因 在美国（79%对51%）和其他国家之间存在显著差异。本研究中具有更侵袭性肿瘤生物学行为的中国人群MAF大于16.93%，表现出 融合事件，且有多个驱动基因突变；因此，这些特征可被视为PTC中的高危基因特征，可能需要对该人群进行积极治疗。
