Martinelli Enrica, Fattorossi Andrea, Battaglia Alessandra, Petrillo Marco, Raspaglio Giuseppina, Zannoni Gian Franco, Fanelli Mara, Gallo Daniela, Scambia Giovanni
Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli -Università Cattolica del Sacro Cuore, Rome, Italy.
Laboratory of Molecular Oncology, Fondazione di Ricerca e Cura Giovanni Paolo II, Campobasso, Italy.
Transl Oncol. 2018 Apr;11(2):358-365. doi: 10.1016/j.tranon.2018.01.016. Epub 2018 Feb 20.
Class III β-tubulin (TUBB3) overexpression in ovarian cancer (OC) associates with poor prognosis. We investigated whether TUBB3 overexpression elicited anti-TUBB3 antibody production in OC patients and whether these antibodies may have diagnostic and prognostic impact. The presence of serum anti-TUBB3 antibodies was investigated in 49 untreated OC patients and 44 healthy individuals by an in-house developed ELISA that used recombinant TUBB3 as the antigen. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of the assay. Anti-TUBB3 antibodies discriminated OC patients and healthy individuals with excellent sensitivity and specificity (91.8% and 90.9%, respectively). In multivariate analysis, anti-TUBB3 antibody level emerged as an independent prognostic factor for progression free and overall survival. The ELISA was then optimized using a biotin-labeled TUBB3 C-terminal peptide instead of recombinant TUBB3 as the antigen and streptavidin-coated plates. The diagnostic role of the anti-TUBB3 antibodies was studied in an independent series of 99 OC patients and 80 gynecological benign disease patients. ROC-curve analysis showed a valuable diagnostic potential for serum anti-TUBB3 antibodies to identify OC patients with higher sensitivity and specificity (95.3% and 97.6%, respectively). Overall, our results provide evidence that preoperative anti-TUBB3 antibody level is a promising diagnostic and prognostic biomarker for the management of OC patients.
III类β微管蛋白(TUBB3)在卵巢癌(OC)中过表达与预后不良相关。我们研究了TUBB3过表达是否会引发OC患者产生抗TUBB3抗体,以及这些抗体是否可能具有诊断和预后意义。通过一种自行开发的以重组TUBB3为抗原的酶联免疫吸附测定(ELISA),对49例未经治疗的OC患者和44名健康个体的血清抗TUBB3抗体进行了检测。绘制受试者工作特征(ROC)曲线以评估该检测方法的诊断准确性。抗TUBB3抗体能够以极高的敏感性和特异性(分别为91.8%和90.9%)区分OC患者和健康个体。在多变量分析中,抗TUBB3抗体水平成为无进展生存期和总生存期的独立预后因素。随后,使用生物素标记的TUBB3 C末端肽替代重组TUBB3作为抗原,并使用链霉亲和素包被的酶标板对ELISA进行了优化。在另一组由99例OC患者和80例妇科良性疾病患者组成的独立队列中,研究了抗TUBB3抗体的诊断作用。ROC曲线分析显示,血清抗TUBB3抗体具有较高的诊断潜力,能够以更高的敏感性和特异性(分别为9`5.3%和97.6%)识别OC患者。总体而言,我们的结果表明术前抗TUBB3抗体水平是管理OC患者的一种有前景的诊断和预后生物标志物。