Department of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Diagn Pathol. 2019 Jul 12;14(1):74. doi: 10.1186/s13000-019-0849-6.
To determine the relevance of the single or combination mutations of BRAF V600E, TERT, and NRAS genes and the clinicopathologic relationship in papillary thyroid cancer (PTC).
Patients with PTC were enrolled into the study between February 2018 and April 2019. Based on the number of mutant genes, we classified the participants into single BRAF V600E mutation group, double mutations group and no mutation group. Single factor and multiple logistic regression analyses were applied to explore the independent factors. Review Manager 5.3 was used for meta-analysis to review the clinical efficacy of gene co-mutations.
Finally, 483 patients were enrolled into the study and 419 (86.7%) of them harbored BRAF V600E mutation. TERT or NRAS mutation was likely to coexist with BRAF V600E mutation in PTC. BRAF V600E and NRAS promoter co-mutations was identified in 6 patients, with a prevalence of 1.2%. Prevalence of BRAF V600E and TERT coexistence in PTC was 2.1%. Significant differences were found among age, pathology, multifocality, bilateral lesions, lymph node metastasis, and 131I radiotherapy, P < 0.01. Multiple logistic regression analyses demonstrated that age [odds ratio (OR) = 1.044, 95% confidence interval (CI) = 1.013-1.076; P = 0.006], lymph node metastasis [OR = 0.094, 95% CI = 0.034-0.264; P < 0.001], 131I radiotherapy [OR = 7.628, 95% CI = 2.721-21.378; P < 0.001] were risk factors for BRAF V600E mutation. Besides, age [OR = 1.135, 95% CI = 1.069-1.205; P < 0.001], multiple leisions [OR = 4.128, 95% CI = 1.026-16.614; P = 0.046], pathology [OR = 3.954, 95% CI = 1.235-12.654; P = 0.021] were independent factors for combination mutations. Meta-analysis showed significant association of BRAF V600E+/TERT+ co-mutations with lymph node metastasis, multifocality, distant metastasis, tumor recurrence, extrathyroidal extension, and dead of disease.
Prevalence of BRAF V600E mutation in Northwest China was higher than other areas. Age, multiple lesions, and pathology were independent factors for double mutation of BRAF V600E/TERT or BRAF V600E/NRAS. Coexistence of BRAF V600E and TERT promoter mutations was significantly correlated with poor outcome.
为了确定 BRAF V600E、TERT 和 NRAS 基因的单一或组合突变与甲状腺乳头状癌（PTC）的临床病理相关性。
2018 年 2 月至 2019 年 4 月期间，我们招募了 PTC 患者入组研究。根据突变基因的数量，我们将参与者分为单 BRAF V600E 突变组、双突变组和无突变组。应用单因素和多因素逻辑回归分析来探讨独立因素。采用 Review Manager 5.3 对基因共突变的临床疗效进行荟萃分析。
最终，483 例患者入组研究，其中 419 例（86.7%）存在 BRAF V600E 突变。TERT 或 NRAS 突变可能与 PTC 中的 BRAF V600E 突变同时存在。在 6 例患者中发现 BRAF V600E 和 NRAS 启动子共突变，占 1.2%。PTC 中 BRAF V600E 和 TERT 共存的发生率为 2.1%。年龄、病理学、多灶性、双侧病变、淋巴结转移和 131I 放疗之间存在显著差异，P<0.01。多因素逻辑回归分析表明，年龄[比值比（OR）=1.044，95%置信区间（CI）=1.013-1.076；P=0.006]、淋巴结转移[OR=0.094，95%CI=0.034-0.264；P<0.001]、131I 放疗[OR=7.628，95%CI=2.721-21.378；P<0.001]是 BRAF V600E 突变的危险因素。此外，年龄[OR=1.135，95%CI=1.069-1.205；P<0.001]、多发病灶[OR=4.128，95%CI=1.026-16.614；P=0.046]、病理学[OR=3.954，95%CI=1.235-12.654；P=0.021]是 BRAF V600E 联合突变的独立因素。荟萃分析显示，BRAF V600E+/TERT+共突变与淋巴结转移、多灶性、远处转移、肿瘤复发、甲状腺外延伸和疾病死亡显著相关。
中国西北地区 BRAF V600E 突变的发生率高于其他地区。年龄、多发病灶和病理学是 BRAF V600E/TERT 或 BRAF V600E/NRAS 双突变的独立因素。BRAF V600E 和 TERT 启动子突变的共存与不良预后显著相关。
