Baron A T, Lafky J M, Suman V J, Hillman D W, Buenafe M C, Boardman C H, Podratz K C, Perez E A, Maihle N J
Tumor Biology Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1175-85.
Soluble ErbB (sErbB) growth factor receptors are being investigated as cancer biomarkers. Gonadotropic and steroid hormones have been shown to modulate the expression of ERBB family members in vivo. Accordingly, the range of sErbB1 values and their relationship to gonadotropic and steroid hormones need to be established in healthy subjects to provide a baseline for future clinical studies. We assayed sera from healthy men and women to determine p110 sErbB1 concentrations by acridinium-linked immunosorbent assay (ALISA). Follicle-stimulating hormone (FSH), estradiol, and testosterone concentrations were measured using the ACS:180 Immunoassay Analyzer. Luteinizing hormone (LH) and progesterone concentrations were quantified using the Access Immunoassay System. Unadjusted for age, p110 sErbB1 concentrations in healthy men and women do not differ significantly. However, sErbB1 concentrations show a strong age-gender interaction, increasing with age in men but decreasing with age in women. Consequently, sErbB1 concentrations are significantly higher in premenopausal women compared with either postmenopausal women or age-matched men and in age-matched men compared with postmenopausal women. Serum sErbB1 concentrations show significant negative associations with both FSH and LH concentrations in healthy women and a significant positive association with FSH concentrations in healthy men. Univariate linear regression models show that these respective gonadotropic hormones and age are independent predictors of sErbB1 concentrations in men and women. Multivariate models show that when age and FSH and LH concentrations are mutually adjusted for each other, they account for 22% of the variability observed in sErbB1 concentrations in healthy women. These data support the hypothesis that gonadotropic and steroid hormones may modulate ERBB1 expression in vivo and suggest that age- and gonadotropin-adjusted sErbB1 concentrations may be of clinical utility. Furthermore, these data demonstrate that gender, age, menstrual cycle phase, menopausal status, and exogenous hormone use must be considered when using serum p110 sErbB1 concentrations as cancer biomarkers.
可溶性表皮生长因子受体(sErbB)正作为癌症生物标志物进行研究。促性腺激素和类固醇激素已被证明可在体内调节ERBB家族成员的表达。因此,需要在健康受试者中确定sErbB1值的范围及其与促性腺激素和类固醇激素的关系,以便为未来的临床研究提供基线。我们检测了健康男性和女性的血清,通过吖啶鎓标记免疫吸附测定法(ALISA)测定p110 sErbB1浓度。使用ACS:180免疫测定分析仪测量促卵泡激素(FSH)、雌二醇和睾酮浓度。使用Access免疫测定系统定量促黄体生成素(LH)和孕酮浓度。未校正年龄时,健康男性和女性的p110 sErbB1浓度无显著差异。然而,sErbB1浓度显示出强烈的年龄-性别相互作用,在男性中随年龄增加而升高,在女性中随年龄增加而降低。因此,绝经前女性的sErbB1浓度显著高于绝经后女性或年龄匹配的男性,年龄匹配的男性的sErbB1浓度也高于绝经后女性。健康女性血清sErbB1浓度与FSH和LH浓度均呈显著负相关,健康男性血清sErbB1浓度与FSH浓度呈显著正相关。单变量线性回归模型显示,这些促性腺激素和年龄分别是男性和女性sErbB1浓度的独立预测因子。多变量模型显示,当年龄与FSH和LH浓度相互校正时,它们可解释健康女性sErbB1浓度中观察到的22%的变异性。这些数据支持促性腺激素和类固醇激素可能在体内调节ERBB1表达的假设,并表明年龄和促性腺激素校正后的sErbB1浓度可能具有临床应用价值。此外,这些数据表明,在将血清p110 sErbB1浓度用作癌症生物标志物时,必须考虑性别、年龄、月经周期阶段、绝经状态和外源激素使用情况。