BRAFV600E突变与甲状腺乳头状癌侵袭性及疗效的相关性分析

Correlation analysis between BRAFV600E mutation and invasiveness and curative effect of papillary thyroid carcinoma

  • 摘要:
    目的  探讨B-Raf原癌基因丝/苏氨酸蛋白激酶(BRAF)V600E基因突变与甲状腺乳头状癌(PTC)临床特征的相关性,并评估其对131I治疗疗效的预后价值。
    方法 回顾性分析2018年4月至2023年4月在天津医科大学总医院接受131I治疗的291例PTC患者的临床资料,其中男性100例,女性191例,年龄(43.4±12.8)岁,范围18~74岁。根据BRAFV600E基因检测结果将患者分为突变型组和野生型组。参照《美国癌症联合会第八版TNM分期标准》对患者进行病理分期。根据患者体重指数和《中国成人超重和肥胖症预防控制指南》将患者分为体重过低组(BMI<18.5 kg/m2)、体重正常组(18.5 kg/m2≤BMI<24.0 kg/m2)、超重组(24.0 kg/m2≤BMI<28.0 kg/m2)、肥胖组(BMI≥28.0 kg/m2)。参照《131I治疗分化型甲状腺癌指南(2021版)》,将疗效评估结果分为疗效满意(ER)、疗效不确切(IDR)、生化疗效不佳(BIR)、结构性疗效不佳(SIR)。计量资料的组间比较采用两独立样本t检验或Mann-Whitney U检验。多组间比较采用单因素方差分析或Kruskal-Wallis H检验。计数资料的组间比较采用χ2 检验。采用多因素Logistic回归分析分析BRAFV600E基因突变及疗效评价的影响因素。
    结果 突变型组较野生型组男性比例更高(χ2=6.55,P=0.007),脉管癌栓比例更低(χ2=10.94,P=0.004)。野生型组N分期更高(χ2=15.41,P<0.001),远处转移率更高(χ2管癌栓比例更低16.25,P=0.001)。治疗后1年疗效评价结果显示,突变型组达到ER、BIR的比例高于野生型组,达到SIR、IDR的比例低于野生型组,差异有统计学意义(χ2=8.79;P=0.032)。多因素Logistic回归分析结果显示:男性BRAFV600E突变风险是女性的2.298倍(OR:2.298,95%CI:1.201~4.395,P=0.012)。半年疗效评价:131I治疗与手术的时间间隔每增加1个月,达到SIR(相较于ER)的风险增加8.1%(OR=1.081,95%CI:1.014~1.153;P=0.017);3年疗效评价:年龄每增加1岁,达到BIR(相较于ER)的风险增加16.2% (OR=1.162,95%CI:1.001~1.349;P=0.048)。
    结论 BRAFV600E基因突变仅与性别相关(男性风险更高),是其独立危险因素,与PTC侵袭性增强及更差的疗效无明确相关性。年龄是影响中期(3年)疗效的关键因素。在手术伤口愈合良好的情况下,应缩短131I治疗与手术的时间间隔以优化短期(半年)疗效。

     

    Abstract:
    Objective To investigate the correlation between the B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation and the clinical characteristics of papillary thyroid cancer (PTC), and to assess its significance and value in evaluating the efficacy of 131I therapy.
    Methods A retrospective analysis was conducted on the clinical data of 291 PTC patients who underwent 131I therapy at our hospital from April 2018 to April 2023. Based on the results of the BRAFV600E genetic test, the patients were divided into the BRAFV600E mutation group and the BRAFV600E wild-type group. According to the 2021 guidelines for the efficacy classification of 131I therapy in differentiated thyroid cancer, patients were classified into four groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). The correlation between BRAFV600E mutation, other factors, and the invasiveness and efficacy of PTC was analyzed using independent sample t-test, Mann-Whitney U test, Kruskal-Wallis test, and chi-square test. Logistic regression analysis was used to identify factors influencing BRAFV600E gene mutation and efficacy evaluation.
    Results The mutation group had a higher proportion of males and a lower probability of vascular invasion compared to the wild-type group (χ2=6.55, 10.94; P=0.007, 0.004). Wild-type group had higher N stages and were more likely to develop distant metastases (χ2=15.41, 16.25; P=0.000, 0.001). The proportion of patients achieving ER at 1 year was significantly higher in the mutation group, while the proportion achieving SIR was significantly lower compared to the wild-type group (χ2=8.79; P=0.032). The probability of BRAFV600E gene mutation in male PTC patients was twice that of females (OR: 1.910, 95% CI: 0.228-0.832; P=0.012). In the 6-month efficacy evaluation, for each month increase in the interval between 131I therapy and surgery, the probability of achieving SIR compared to ER increased by a factor of 1 (OR: 1.081, 95% CI: 1.014-1.153; P=0.017). In the 3-year efficacy evaluation, for each year increase in age, the probability of achieving BIR compared to ER increased by a factor of 1 (OR: 1.162, 95% CI: 1.001-1.349; P=0.048).
    Conclusions Gender is the sole independent risk factor associated with the BRAFV600E mutation. There is no clear correlation between BRAFV600E gene mutation and greater invasiveness or poorer curative effect of PTC. Age is a critical determinant of mid-term therapeutic efficacy. When wound healing is satisfactory, the interval between 131I therapy and surgery should be minimized to achieve better short-term efficacy.

     

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