Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.
Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.
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DOI：
10.1093/jnci/djp438
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发表时间：
2010-01-06
期刊：
影响因子：
--
通讯作者：
Urban N
中科院分区：
文献类型：
--
作者：
Anderson GL;McIntosh M;Wu L;Barnett M;Goodman G;Thorpe JD;Bergan L;Thornquist MD;Scholler N;Kim N;O'Briant K;Drescher C;Urban N
CA125、人附睾蛋白 4 (HE4)、间皮素、B7-H4、诱饵受体 3 (DcR3) 和 spondin-2 已被确定为潜在的卵巢癌生物标志物。除 CA125 外，尚未对它们在诊断前的行为进行评估。使用免疫测定法测定诊断前血清样本（每个参与者 1-11 个样本）中 CA125、HE4、间皮素、B7-H4、DcR3 和 spondin-2 蛋白的浓度，这些样本来自 34 名卵巢癌患者（其中 15 名患有晚期浆液性癌）在卵巢癌诊断前 0-18 年以及在参考日期之前 70 年的可比时间间隔内提供 匹配参加胡萝卜素和视黄醇功效试验的对照受试者。洛斯曲线分别与癌症患者和对照受试者的生物标志物水平进行拟合，以总结随时间变化的平均水平。绘制受试者工作特征曲线，并计算曲线下面积（AUC）统计数据，以总结这些生物标志物在诊断前时间的辨别能力。相对于对照受试者，癌症患者的 CA125、HE4 和间皮素（但不是 B7-H4、DcR3 和 spondin-2）的平滑平均浓度在诊断前大约 3 年开始（视觉上）增加，但仅在诊断前最后一年才达到可检测到的升高。在描述性受试者操作特征分析中，这些生物标志物的区分能力有限（AUC统计范围 = 0.56-0.75），但随着诊断时间的临近，其准确性不断提高（例如，诊断前 ≥4 年、2-4 年和 <2 年时，CA125 的 AUC 统计数据分别为 0.57、0.68 和 0.74）。 CA125、HE4 和间皮素的血清浓度可能在临床诊断前 3 年提供卵巢癌的证据，但与这些标志物相关的可能提前期似乎不到 1 年。
CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated. Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1–11 samples per participant) that were contributed 0–18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial. Lowess curves were fit to biomarker levels in cancer patients and control subjects separately to summarize mean levels over time. Receiver operating characteristic curves were plotted, and area-under-the curve (AUC) statistics were computed to summarize the discrimination ability of these biomarkers by time before diagnosis. Smoothed mean concentrations of CA125, HE4, and mesothelin (but not of B7-H4, DcR3, and spondin-2) began to increase (visually) in cancer patients relative to control subjects approximately 3 years before diagnosis but reached detectable elevations only within the final year before diagnosis. In descriptive receiver operating characteristic analyses, the discriminatory power of these biomarkers was limited (AUC statistics range = 0.56–0.75) but showed increasing accuracy with time approaching diagnosis (eg, AUC statistics for CA125 were 0.57, 0.68, and 0.74 for ≥4, 2–4, and <2 years before diagnosis, respectively). Serum concentrations of CA125, HE4, and mesothelin may provide evidence of ovarian cancer 3 years before clinical diagnosis, but the likely lead time associated with these markers appears to be less than 1 year.
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影响因子：
120.7
作者：
HELZLSOUER, KJ;BUSH, TL;COMSTOCK, GW
通讯作者：
COMSTOCK, GW
影响因子：
6.4
作者：
Belisle, Jennifer A.;Gubbels, Jennifer A. A.;Patankar, Manish S.
通讯作者：
Patankar, Manish S.
影响因子：
8.4
作者：
BERRUTI, A;TAMPELLINI, M;DOGLIOTTI, L
通讯作者：
DOGLIOTTI, L
影响因子：
9.7
作者：
Bergan, Lindsay;Gross, Jennifer A.;Scholler, Nathalie
通讯作者：
Scholler, Nathalie
影响因子：
4.4
作者：
Faca, Vitor;Pitteri, Sharon J.;Hanash, Samir
通讯作者：
Hanash, Samir