Hermann Natalie, Dressen Katja, Schroeder Lars, Debald Manuel, Schildberg Frank A, Walgenbach-Bruenagel Gisela, Hettwer Karina, Uhlig Steffen, Kuhn Walther, Hartmann Gunther, Holdenrieder Stefan
1 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
2 Department of Gynecology and Obstetrics, University Hospital Bonn, Bonn, Germany.
Tumour Biol. 2017 Jun;39(6):1010428317711381. doi: 10.1177/1010428317711381.
Multiple factors contribute to the development and progression of breast cancer. Markers of tumor growth and invasion, cell death, immune activation, and angiogenesis can be assessed in parallel by a novel multiplex immunoassay panel. The diagnostic performance of a multiplex cancer biomarker magnetic bead panel comprising 24 tumor associated parameters was evaluated in sera of 154 women including 77 patients with breast cancer, 10 with precancerous lesions, 31 with benign breast diseases, and 36 healthy controls. Marker levels were log-transformed for variance stabilization. Significance testing was done using t-test or Wilcoxon rank-sum test with correction of p values for multiple testing. Furthermore, receiver operating characteristic analyses were performed. Serum levels of several biomarkers were significantly (p ≤ 0.001) higher in cancer patients than in healthy controls, particularly alpha-fetoprotein, cancer antigen 15-3, cancer antigen 19-9, migration inhibitory factor, carcinoembryonic antigen, cancer antigen 125, hepatocyte growth factor, soluble Fas, tumor necrosis factor-α, stem cell factor, and osteopontin. As most markers were also elevated in benign breast diseases, only cancer antigen 15-3 showed significant differences to cancer patients (p ≤ 0.001). The resulting areas under the curve in receiver operating characteristic curves for discrimination between benign and malignant breast diseases achieved 0.71 with a sensitivity of 33.8% at 95% specificity. Multiplexing enables parallel analysis of different biomarker classes for cancer detection. Established cancer antigen 15-3 proved to be most relevant for differential diagnosis.
多种因素促成了乳腺癌的发生和发展。肿瘤生长与侵袭、细胞死亡、免疫激活及血管生成的标志物可通过一种新型多重免疫分析检测板进行并行评估。在154名女性的血清中评估了包含24个肿瘤相关参数的多重癌症生物标志物磁珠检测板的诊断性能，其中包括77例乳腺癌患者、10例癌前病变患者、31例良性乳腺疾病患者及36名健康对照者。为使方差稳定，对标志物水平进行对数转换。采用t检验或Wilcoxon秩和检验进行显著性检验，并对多重检验的p值进行校正。此外，还进行了受试者工作特征分析。癌症患者血清中几种生物标志物的水平显著高于健康对照者（p≤0.001），尤其是甲胎蛋白、癌抗原15-3、癌抗原19-9、迁移抑制因子、癌胚抗原、癌抗原125、肝细胞生长因子、可溶性Fas、肿瘤坏死因子-α、干细胞因子及骨桥蛋白。由于大多数标志物在良性乳腺疾病中也升高，只有癌抗原15-3与癌症患者有显著差异（p≤0.001）。在区分良性和恶性乳腺疾病的受试者工作特征曲线中，曲线下面积为0.71，在95%特异性时灵敏度为33.8%。多重检测能够对不同生物标志物类别进行并行分析以用于癌症检测。已证实，既定的癌抗原15-3在鉴别诊断中最为相关。
