Lokshin Anna E, Winans Mathew, Landsittel Douglas, Marrangoni Adele M, Velikokhatnaya Lyudmila, Modugno Francesmary, Nolen Brian M, Gorelik Elieser
University of Pittsburgh Cancer Institute, Hillman Cancer Center, University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Gynecol Oncol. 2006 Aug;102(2):244-51. doi: 10.1016/j.ygyno.2005.12.011. Epub 2006 Jan 24.
In an ongoing effort to identify diagnostic ovarian cancer biomarkers, SEREX (serological analysis of recombinant cDNA expression libraries) technique was employed resulting in detection of 20 known genes, nine ESTs and one novel sequence. Interleukin-8 (IL-8) was one of ovarian cancer-associated antigens identified by SEREX screening. The objective of this study was, therefore, to evaluate the potential importance of circulating anti-IL-8 antibody as ovarian cancer biomarker.
We developed and optimized a new immunofluorescent bead-based assay for detection of anti-IL-8 antibody in blood serum. Circulating IL-8 and anti-IL-8 IgG concentrations were measured in blood sera from 44 patients with early stage (I-II) ovarian cancer, 50 patients with late stage (III-IV) ovarian cancer, 37 patients with benign pelvic masses, and 80 healthy women using the bead-based assay.
Our data indicate that serum contains IL-8 cytokine, anti-IL-8 antibody, and IL-8:anti-IL-8 complexes. We found that concentrations of IL-8 and anti-IL-8 antibody were elevated in sera of patients with ovarian cancer as compared with healthy controls. Logistic regression analysis of circulating concentrations of anti-IL-8 IgG in patients with stages I-II ovarian cancer versus healthy controls allowed for prediction of early ovarian cancer with 98% specificity, 65.5% sensitivity, 80.3% of patients correctly classified. Combining IL-8 and anti-IL-8 IgG with CA 125 resulted in increased classification power as compared to individual markers analyzed separately.
Thus, IL-8 and anti-IL-8 autoantibody might potentially serve as additional biomarkers for ovarian cancer.
为了持续寻找诊断卵巢癌的生物标志物，采用了SEREX（重组cDNA表达文库血清学分析）技术，结果检测到20个已知基因、9个EST和1个新序列。白细胞介素-8（IL-8）是通过SEREX筛选鉴定出的卵巢癌相关抗原之一。因此，本研究的目的是评估循环抗IL-8抗体作为卵巢癌生物标志物的潜在重要性。
我们开发并优化了一种基于免疫荧光微珠的新方法，用于检测血清中的抗IL-8抗体。使用基于微珠的检测方法，测量了44例早期（I-II期）卵巢癌患者、50例晚期（III-IV期）卵巢癌患者、37例盆腔良性肿块患者和80名健康女性血清中的循环IL-8和抗IL-8 IgG浓度。
我们的数据表明，血清中含有IL-8细胞因子、抗IL-8抗体和IL-8：抗IL-8复合物。我们发现，与健康对照组相比，卵巢癌患者血清中IL-8和抗IL-8抗体的浓度升高。对I-II期卵巢癌患者与健康对照组的抗IL-8 IgG循环浓度进行逻辑回归分析，预测早期卵巢癌的特异性为98%，敏感性为65.5%，正确分类的患者为80.3%。与单独分析的单个标志物相比，将IL-8和抗IL-8 IgG与CA 125结合可提高分类能力。
因此，IL-8和抗IL-8自身抗体可能作为卵巢癌的额外生物标志物。
