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131I治疗甲状腺功能亢进症(简称甲亢)的疗效好、复发率低,治愈率高达80%~90%,已成为临床治疗甲亢的主要方法[1]。有学者指出131I治疗甲亢的效果除了与患者病史、性别、年龄、吸碘率、甲状腺质量、有效半减期等有关外,辐射敏感的个体差异性可能起到关键作用。目前研究表明,个体对射线的敏感性是由一系列修复DNA损伤的基因群的表达程度所决定的[2]。其中,表皮生长因子受体(epidermal growth factor receptor,EGFR)是跨膜受体酪氨酸激酶的一种,在调节肿瘤细胞增殖及细胞周期进程中发挥着重要作用[3-4]。有文献报道,EGFR通过参与辐射治疗过程中细胞增殖反应、辐射诱导的DNA损伤修复等途径参与辐射抵抗[5-6]。鉴于外照射与内照射在辐射生物效应方面的相似性,有理由认为EGFR的表达与131I治疗甲亢之间可能存在某些联系,但目前国内外尚未发现EGFR基因表达与131I治疗甲亢疗效关系的相关报道。因此,本研究应用实时定量PCR法检测甲亢组织中EGFR基因的表达,探讨EGFR基因表达与甲亢131I治疗疗效的可能关系。
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59例甲亢患者经131I治疗后6个月,失访8例,其余患者中,甲减占39.2%(20/51),完全缓解占41.2%(21/51),未愈占19.6%(10/51),甲亢治愈率(甲减+完全缓解)为80.4%(41/51)。
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EGFR在正常甲状腺组织及甲亢患者组织中都有不同程度的表达。甲亢患者组织中EGFR的相对表达水平明显高于正常组织(1.752±0.660 vs. 0.859±0.125,t=4.328,P<0.001)。所有患者采用计算剂量法一次性口服131I治疗随访6个月后,根据分组方案1:未愈组EGFR相对表达水平显著高于治愈组(8.092±3.887 vs. 1.383±0.160,t=7.647,P<0.001)。根据分组方案2:未愈组(8.092±3.887)EGFR相对表达水平高于完全缓解组(1.487±0.479)和甲减组(0.968±0.180)(t=7.364和8.027,P<0.001)。完全缓解组EGFR相对表达水平高于甲减组(1.487±0.479 vs. 0.968±0.180,t=1.427,P>0.05),差异无统计学意义。
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将性别、年龄、病程、甲状腺激素水平、甲状腺球蛋白抗体、甲状腺微粒体抗体、24 h甲状腺最高摄碘率、甲状腺有效半衰期、甲状腺质量、口服131I剂量等临床特征量化,并将EGFR相对表达量作为因变量,是否治愈作为结果变量引入多因素方程,应用逐步向后剔除法筛选变量,对全部原因变量进行Logistic回归分析,结果被引入回归方程的影响因素只有EGFR、131I剂量和甲状腺质量(表 1)。
观察因素 回归系数 标准误 OR值 95%CI P值 EGFR 0.335 0.281 1.423 1.233 0.048 131I剂量 -0.901 0.485 3.456 0.401 0.025 甲状腺质量 0.092 0.047 3.853 1.096 0.040 常数 -1.129 1.237 0.832 0.323 - 注:表中,“ -”表示此处无数据。 表 1 Logistic回归方程中的变量和常数
Table 1. Variables and constants in the logistic regression equation
表皮生长因子受体基因表达与甲状腺功能亢进症131I治疗预后的关系
The relationship between epidermal growth factor receptor mRNA expression and the efficacy of 131I treatment in hyperthyroidism patients
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摘要: 目的探讨甲状腺功能亢进症(简称甲亢)组织中表皮生长因子受体(EGFR)基因相对表达与131I治疗预后的关系。方法入组拟行131I治疗的59例Graves甲亢患者作为实验组,平均年龄(46.46±12.95)岁,其中男性16例、女性43例;正常对照组27名,平均年龄(44.66±10.86)岁,其中男性6名、女性21名。入选者采用细针穿刺法获取甲状腺组织,应用荧光实时定量PCR法检测甲亢组织及正常甲状腺组织中EGFR基因的相对表达水平,采用t检验、方差分析及多因素分析探讨EGFR基因相对表达水平与131I治疗预后的关系。结果EGFR基因在正常甲状腺组织及Graves甲亢组织中都有不同程度的表达;甲亢组织中EGFR的相对表达水平明显高于正常甲状腺组织(1.752±0.660 vs. 0.859±0.125,t=4.328, P<0.001)。59例Graves甲亢患者经131I治疗6个月后,失访8例,其中,甲状腺功能减退症(简称甲减)占39.2%(20/51)、完全缓解占41.2%(21/51)、未愈占19.6%(10/51),甲亢治愈率(甲减+完全缓解)为80.4%。未愈组EGFR相对表达水平显著高于治愈组(甲减+完全缓解)(8.092±3.887 vs. 1.383±0.160, t=7.647,P<0.001);未愈组(8.092±3.887)EGFR相对表达水平高于完全缓解组(1.487±0.479)和甲减组(0.968±0.180)(t=7.364和8.027, P<0.001)。Logistic回归分析显示:口服131I剂量(OR=3.456)、甲状腺质量(OR=3.853)及EGFR相对表达水平(OR=1.423)是甲亢患者131I治疗后影响治疗效果的主要因素。结论EGFR基因的相对表达可能是预测甲亢131I治疗近期疗效及预后的指标。Abstract: Objective To study the relationship between the epidermal growth factor receptor(EGFR)mRNA expression and the efficacy of 131I treatment in hyperthyroidism patients. Methods Fine needle biopsies of 59[the male to female ratio was 16:43; mean age was(46.46±12.95) years old] Graves disease patients and 27[the male to female ratio was 6:21; mean age was(44.66±10.86) years old] normal volunteers were collected. The mRNA expression of EGFR was detected by real-time polymerase chain reaction before treatment. T-test, analysis of variance and multivariate logistic regression analysis were applied to analyze the relationship between EGFR mRNA expression and the efficacy of 131I treatment. Results Compared with normal group, the mRNA expression level of EGFR was significantly higher in Graves disease patients(1.752±0.660 vs. 0.859±0.125, t=4.328, P < 0.001). Six months after 131I treatment, except 8 cases were lost in following up, all of the remain 51 eligible evaluated patients were relieived from hyperthyroidism. Among them, 80.4% of patients was cured, 39.2%(20/51) became hypothyroid, 41.2%(21/51) became euthyroid, and 19.6%(10/51) remained hyperthyroid. The EGFR mRNA expression was significantly higher in uncured group than in cured group(8.092±3.887 vs. 1.383±0.160, t=7.647, P < 0.001). The EGFR mRNA expression was significantly higher in uncured group(8.092±3.887) than in euthyroid(1.487±0.479)or hypothyroid group(0.968±0.180)(t=7.364 and 8.027, P < 0.001). Multiple logistic regression revealed that the radioiodine dosage(OR=3.456), thyroid weight(OR=3.853) and EGFR mRNA expression(OR=1.423) was related to the efficacy of 131I treatment. Conclusion EGFR mRNA expression may be used in evaluating the prognosis of hyperthyroidism patients after 131I treatment.
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Key words:
- Hyperthyroidism /
- Iodine radioisotopes /
- Receptor, epidermal growth factor /
- Prognosis
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表 1 Logistic回归方程中的变量和常数
Table 1. Variables and constants in the logistic regression equation
观察因素 回归系数 标准误 OR值 95%CI P值 EGFR 0.335 0.281 1.423 1.233 0.048 131I剂量 -0.901 0.485 3.456 0.401 0.025 甲状腺质量 0.092 0.047 3.853 1.096 0.040 常数 -1.129 1.237 0.832 0.323 - 注:表中,“ -”表示此处无数据。 -
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