BRAF^(V600E)基因突变与甲状腺乳头状癌超声及临床病理特征的相关性

Correlation Between BRAF^(V600E) Gene Mutation and Ultrasonographic and Clinicopathological Features of Papillary Thyroid Carcinoma

目的:探讨BRAF^(V600E)基因突变与甲状腺乳头状癌患者常规超声及临床病理特征的相关性。方法:选取2021年07月-2022年07月经石河子大学第一附属医院胃肠甲状腺外科收治行手术治疗,术后病理明确诊断为甲状腺乳头状癌(Papillary Thyroid Carcinoma,PTC)的患者187例,提取患者术前穿刺标本或术后石蜡包埋组织DNA,利用实时荧光PCR定量技术进行BRAF^(V600E)基因检测,根据基因检测结果分为BRAF^(V600E)基因突变阳性组和BRAF^(V600E)基因突变阴性组,收集187例PTC患者的常规超声特征及临床病理资料,分析其与BRAF^(V600E)基因突变的相关性。采用多因素二元Logistic回归分析以确定发生BRAF^(V600E)基因突变的独立危险因素,以多因素二元Logistic回归分析中有统计学意义的指标建立BRAF^(V600E)基因突变的预测模型,并采用受试者工作特征(Receiver Operating Characteristic curve,ROC)曲线对模型的预测效能进行评价。结果:187例患者中BRAF^(V600E)基因突变阳性患者144例(77.0%),BRAF^(V600E)基因阴性患者43例(23.0%)。两组患者在是否伴桥本甲状腺炎、形态、钙化、中央淋巴结转移情况、抗甲状腺过氧化酶抗体、抗甲状腺球蛋白抗体、ki-67这7项指标的比较差异具有统计学意义(P<0.05);二元Logistic回归分析结果显示,不伴桥本甲状腺炎(OR=3.015)、形态不规则(OR=2.694)、伴中央淋巴结转移(OR=2.685)、ki-67≥4.5%(OR=3.084)是PTC患者发生BRAF^(V600E)基因突变的独立危险因素(P<0.05)。采用二元Logistic回归分析方法建立的预测方程为:Logit(P)=In(P/1-P)=-0.968+1.104×桥本甲状腺炎+0.991×形态+0.988×中央淋巴结转移情况+1.126×ki-67。对预测模型进行效能检验,预测模型的ROC曲线下面积为0.808,模型的预测效能中等。结论:不伴桥本甲状腺炎、结节形态不规则、伴中央淋巴结转移、ki-67≥4.5%是甲状腺乳头状癌患者发生BRAF^(V600E)基因突变的独立危险因素,上述特征可以用来预测BRAF^(V600E)基因突变情况,本研究建立的BRAF^(V600E)基因突变预测模型对PTC患者的临床诊治及预后评估有一定指导意义。

Objective:To investigate the correlation between BRAF^(V600E) gene mutation and conventional ultrasound and clinicopathological features in patients with papillary thyroid carcinoma.Methods:Selected from July 2021-July 2022,through the treatment of surgery of the first affiliated hospital of Shihezi University,postoperative pathological diagnosis of 187 patients with Papillary Thyroid Carcinoma(PTC),extracting patients with patients or surgery After the paraffin buried tissue DNA,use real-time fluorescent PCR quantitative technology to perform the BRAF^(V600E) gene test.According to the genetic test results,it is divided into the BRAF^(V600E) gene mutation positive group and the BRAF^(V600E) gene mutation negative group.Analyze the correlation between its mutation with the BRAF^(V600E) gene.Adopt multi-factor dual Logistic regression analysis to determine the independent risk factors that occur in the BRAF^(V600E) gene mutation and establish a predictive model of the BRAF^(V600E) gene mutation based on the multi-factor dual Logistic regression analysis and use the Receiver Operating Characteristic(ROC)Curve evaluate the predictive effectiveness of the model.Results:Among 187 patients,144 patients with BRAF^(V600E) gene mutations(77.0%),and 43 patients with BRAF^(V600E) gene negative patients(23.0%).Whether the two groups of patients are accompanied by bridges,form,calcification,central lymph node metastasis,anti-thyroid peroxidase antibodies,anti-thyroid globulin antibodies,and ki-67(P<0.05).The results of binary Logistic regression analysis showed that do not accompany bridge thyroiditis(OR=3.015),irregular morphology(OR=2.694),central lymph nodes transfer(OR=0.685),ki-67≥4.5%(OR=3.084)It is an independent risk factor for the BRAF^(V600E) gene mutation in PTC patients(P<0.05).The prediction equation established by the binary Logistic regression analysis method is:Logit(P)=In(P/1-P)=-0.968+1.104×Hashimoto thyroiditis+0.991×morphology+0.988×central lymph node metastasis status+1.126×ki-67.The effectiveness test of the predictive model is performed,and the area under the ROC curve of the predicted model is 0.808,and the predictive effectiveness of the model is moderate.Conclusion:Without Hashimoto's thyroiditis,irregular shape,central lymph node metastasis and ki-67≥4.5%are independent risk factors for BRAF^(V600E) gene mutation in patients with papillary thyroid carcinoma.The above characteristics can be used to predict BRAF^(V600E) gene mutation.The prediction model of BRAF^(V600E) gene mutation established in this study has certain guiding significance for the clinical diagnosis,treatment,and prognosis evaluation of PTC patients.