Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cancer. 2012 Jan 1;118(1):91-100. doi: 10.1002/cncr.26241. Epub 2011 Jun 29.
When epithelial ovarian cancer is detected at an early stage (I-II), the 5-year survival rate is between 70% and 90%; whereas, when it is detected in late stages (III-IV), the 5-year survival rate slips to <30%. In a previous report, the authors observed that proteomic biomarkers and cancer antigen 125 (CA 125) exhibited a sensitivity of 84% at a specificity of 98% for identifying sera from patients who had stage I disease at the time of surgery, significantly improving the sensitivity of CA 125 alone. The challenge, however, is to detect ovarian cancer before clinical diagnosis. The current study was part of a large effort to compare different multimarker biomarker panels for the early detection of ovarian cancer. Several biomarkers were evaluated alone and in combination with CA 125 in prediagnostically collected sera from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Proximal prediagnostic sera from 118 women with ovarian cancer (cases) and from 951 age-matched women (controls) (8 controls per case, including 4 randomly selected from the general population, 2 with CA 125 levels ≥ 35 U/mL, and 2 with a positive family history of breast/ovarian cancer) were analyzed using the CA 125 immunoassay and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry to measure 7 proteins (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, β-2 microglobulin, connective tissue activating protein III), and interalpha-trypsin inhibitor heavy-chain 4). Data were analyzed by 2 statistical strategies that combined the 7 markers and CA 125 into 1 predictive score for disease classification.
CA 125 levels were elevated (≥ 35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected <12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone.
In contrast to earlier findings from analyzes of postdiagnostically collected sera, the addition of 7 biomarkers to CA 125 did not improve sensitivity for preclinical diagnosis beyond CA 125 alone.
当上皮性卵巢癌在早期（I-II 期）被检测到时，5 年生存率在 70%至 90%之间；而当在晚期（III-IV 期）被检测到时，5 年生存率下降到<30%。在之前的一份报告中，作者观察到蛋白质组生物标志物和癌症抗原 125（CA 125）在识别手术时处于 I 期疾病的患者血清时具有 84%的灵敏度和 98%的特异性，显著提高了 CA 125 单独的灵敏度。然而，挑战在于在临床诊断之前检测卵巢癌。本研究是比较不同多标志物生物标志物面板用于早期检测卵巢癌的大型研究的一部分。在前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中，在预诊断收集的女性血清中单独评估了几种生物标志物，并与 CA 125 联合评估。
对 118 名卵巢癌患者（病例）和 951 名年龄匹配的女性（对照）（每例 8 名对照，包括 4 名随机选自普通人群、2 名 CA 125 水平≥35 U/mL 和 2 名乳腺癌/卵巢癌阳性家族史）的近预诊断血清进行了分析，使用 CA 125 免疫分析和表面增强激光解吸电离飞行时间质谱法测量了 7 种蛋白质（载脂蛋白 A1、截短转甲状腺素蛋白、转铁蛋白、hepcidin、β-2 微球蛋白、连接组织激活蛋白 III）和 interalpha-trypsin 抑制剂重链 4）。通过 2 种统计策略分析数据，将 7 种标志物和 CA 125 组合成 1 个预测评分用于疾病分类。
在可获得癌症诊断前<12 个月采集的样本中 CA 125 数据的 65 名患者中，有 61.5%的 CA 125 水平升高（≥35 U/mL）；然而，在病例和 3 个对照组中，单独或联合使用另外 7 种生物标志物的水平没有差异。2 个联合 CA 125 和 7 种生物标志物的面板未能提高 CA 125 单独的敏感性。
与之前对诊断后收集的血清进行分析的结果相反，在 CA 125 之外添加 7 种生物标志物并不能提高临床前诊断的敏感性。
