研究动态
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甲状腺癌中 CCDC6-RET 和 NCOA4-RET 融合的临床病理特征:中国人群的单中心回顾性队列研究。

Clinicopathological Features of CCDC6-RET and NCOA4-RET Fusions in Thyroid Cancer: A Single-center Retrospective Cohort Study in a Chinese Population.

发表日期:2024 Aug 30
作者: Zhiting Wang, Qianlan Yao, Longlong Bao, Heng Chang, Min Ren, Tian Xue, Ran Wei, Chengli Yu, Qian Wang, Yu Wang, Bo Ping, Qian-Ming Bai, Xiaoyan Zhou, Xiao-Li Zhu
来源: THYROID

摘要:

转染期间重排(RET)原癌基因融合在甲状腺乳头状癌(PTC)中很常见,不同种族的人群有所不同。然而,RET融合类型的综合比较是有限的。本研究旨在确定中国甲状腺癌病例队列中主要的 RET 融合并分析其临床病理特征。这项单中心回顾性队列研究利用福尔马林固定、石蜡包埋的组织样本的新一代测序分析了甲状腺癌数据。收集了具有RET融合的甲状腺癌病例的详细临床病理资料。在2300例甲状腺癌病例中,RET融合仅见于PTC或分化型高级别甲状腺癌(DHGTC)病例(2234例),其他类型不存在(66例) 。在 2234 例 PTC 或 DHGTC 病例中,113 例(5.06%)表现出 RET 融合,其中包括 100 例原发病例。 CCDC6-RET 融合占主导地位 (78.0%, 78/100),NCOA4-RET 融合占 22.0% (22/100)。 NCOA4-RET 融合在 45 岁及以上患者中更为常见(54.5% vs. 28.2%,P = 0.021)和 DHGTC 病例(P < 0.05),并且与较高的淋巴结转移率相关(90.9% vs. 67.9) %,P = 0.032)。 CCDC6-RET 融合表现出桥本甲状腺炎患病率较高(67.9% vs. 22.7%,P < 0.001),并且甲状腺球蛋白抗体水平升高(14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, P = 0.018)。此外,CCDC6-RET融合主要发生在经典PTC(56.4%,44/78)和浸润性滤泡性PTC(17.9%,14/78)中,而NCOA4-RET融合在经典PTC中更常见(36.4%,8/22) )、固体 PTC(27.3%,6/22)和 DHGTC(27.3%,6/22)。具有复合突变的 RET 融合与年龄较大(≥45 岁)和双侧甲状腺受累有关。随访数据显示,与BRAF V600E突变组相比,RET融合组的复发率较高(5.0% vs. 0.0%,P = 0.018)。虽然 NCOA4-RET 组的复发率在数值上高于 CCDC6-RET(9.1% vs. 3.8%),但这种差异并不具有统计学意义(P = 0.559)。RET 融合是中国甲状腺患者中 PTC 或 DHGTC 病例所特有的。癌症病例。 CCDC6-RET 和 NCOA4-RET 融合表现出不同的临床病理特征,其中 NCOA4-RET 更具侵袭性。
The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases.This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected.Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. CCDC6-RET fusions predominated (78.0%, 78/100), with NCOA4-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, P = 0.021) and DHGTC cases (P < 0.05), and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, P = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (67.9% vs. 22.7%, P < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, P = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classic PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classic PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared to the BRAF V600E mutation group (5.0% vs. 0.0%, P = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared to CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (P = 0.559).RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive.