分化型甲状腺癌中KRAS、BRAF^(V600E)基因突变与^(131)I放射治疗耐受的关系

Relationship between KRAS and BRAF^(V600E) gene mutations and ^(131)I radiotherapy tolerance in differentiated thyroid carcinoma

目的探讨分化型甲状腺癌(DTC)中鼠类肉瘤病毒癌基因(KRAS)、鼠类肉瘤滤过性毒菌致癌基因同源体B(BRAF)基因突变与^(131)I放射治疗耐受的相关性。方法回顾性收集2010年3月—2015年6月于我院接受甲状腺全切除术及术后行^(131)I放射治疗的219例DTC患者的临床资料和病理组织样本,根据患者对^(131)I放射治疗的耐受情况分为耐受组和敏感组,检测病理组织样本中KRAS和BRAF^(V600E)基因的突变情况。结果耐受组年龄≥45岁、甲状腺滤泡状癌(FTC)、远处转移及转移灶≥1 cm的患者比例显著高于敏感组,差异有统计学意义(P<0.05)。KRAS基因突变在FTC中发生率较高,BRAF^(V600E)基因突变在甲状腺乳头状癌(PTC)中发生率较高;此外,KRAS和BRAF^(V600E)基因突变均与原发肿瘤最大直径、AJCC TNM分期、淋巴结转移、腺外侵犯、远处转移及转移灶大小有关(P<0.05)。耐受组KRAS和BRAF^(V600E)基因突变的发生率均显著高于敏感组(P<0.05)。年龄≥45岁、转移灶≥1 cm、KRAS和BRAF^(V600E)基因突变是DTC患者^(131)I放射治疗耐受的独立预测因素(P<0.05)。耐受组5年生存率显著低于敏感组,KRAS突变型患者5年生存率显著低于野生型患者,BRAF^(V600E)突变型患者5年生存率显著低于野生型患者,耐受组KRAS、BRAF^(V600E)突变型患者5年生存率均显著低于野生型患者,差异均有统计学意义(P<0.05)。结论 KRAS基因和BRAF^(V600E)基因突变是导致DTC患者^(131)I放射治疗耐受的独立危险因素,且对患者的预后评估具有重要意义。

Objective To investigate the correlation of^(131)I radiotherapy tolerance with mutations of Kirsten rat sarcoma viral oncogene (KRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) genes in differentiated thyroid cancer(DTC).Methods The clinical data and pathological tissue samples of 219 patients with DTC who received total thyroidectomy and postoperative^(131)I radiotherapy in our hospital between March 2010 and June 2015 were collected retrospectively.Patients were divided into the tolerant group and the sensitive group according to their tolerance to^(131)I radiotherapy.KRAS and BRAF^(V600E)mutations of the pathological tissue samples were detected.Results The proportion of patients with age≥45years,follicular thyroid carcinoma (FTC),distant metastasis and metastatic lesion≥1 cm in the tolerant group was higher than that of the sensitive group (P<0.05).KRAS mutation had a high incidence in FTC,while BRAF^(V600E)mutation had a high incidence in papillary thyroid carcinoma (PTC).In addition,both KRAS and BRAF^(V600E)mutation were associated with the largest diameter of primary tumor,AJCC TNM stage,lymph node metastasis,extraglandular invasion,distant metastasis and the size of metastatic lesions (P<0.05).The incidence of KRAS and BRAF^(V600E)mutations in the tolerant group was higher than that in the sensitive group,with statistically significant differences (P<0.05).Age≥45 years,the size of metastatic lesion≥1 cm,KRAS or BRAF^(V600E)mutation were independent predictors of^(131)I radiotherapy tolerance in DTC patients (P<0.05).The 5-year survival rate was lower respectively in the tolerant group,KRAS mutation group,BRAF^(V600E)mutation group,subgroup with KRAS mutation in tolerant group and subgroup with BRAF^(V600E)mutation in tolerant group (P<0.05).Conclusion KRAS gene and BRAF^(V600E)gene mutation were independent risk factors for^(131)I radiotherapy tolerance in patients with DTC,and had important significance for the prognosis assessment of patients with DTC.