Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.
Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA.
Cancer Biomark. 2020;27(3):407-421. doi: 10.3233/CBM-190988.
The majority of ovarian cancer cases are diagnosed at an advanced stage with poor prognosis. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for early detection of ovarian cancer in women at increased risk.
To assess the immunoreactivity of paraneoplastic antigens and tumor associated antigens with high-grade serous ovarian cancer (HGSOC) samples.
Five paraneoplastic antigens along with three tumor-associated antigens were evaluated with HGSOC patient serum samples. Validation screening was performed with n= 164 serum samples consisting of: 50 late stage HGSOC, 14 early stage HGSOC, 50 benign ovarian cyst, and 50 healthy control samples on ELISA and western blot. The four markers TRIM21, NY-ESO-1, TP53, and PAX8 were evaluated on a second validation serum set, n= 150.
TRIM21 achieved the highest sensitivity in the first validation screening of 33% with 100% specificity. Combining TRIM21 with NY-ESO-1, TP53, and PAX8 provided 67% sensitivity with 94% specificity, and 56% sensitivity at 98% specificity. These four markers resulted in 46% sensitivity with 98% specificity in the second validation cohort; TRIM21 achieved the highest individual sensitivity of 36%.
Autoantibodies to TRIM21, NY-ESO-1, and TP53 may complement CA125 in screening of women at genetic risk for ovarian cancer.
大多数卵巢癌病例在晚期诊断，预后较差。本研究评估了针对肿瘤抗原的自身抗体，以鉴定出高风险女性卵巢癌早期检测的候选生物标志物。
评估副肿瘤抗原和肿瘤相关抗原与高级别浆液性卵巢癌（HGSOC）样本的免疫反应性。
用 HGSOC 患者血清样本评估了 5 种副肿瘤抗原和 3 种肿瘤相关抗原。验证筛选在 n=164 例血清样本中进行，包括：50 例晚期 HGSOC、14 例早期 HGSOC、50 例良性卵巢囊肿和 50 例健康对照组，采用 ELISA 和 Western blot 进行检测。TRIM21、NY-ESO-1、TP53 和 PAX8 这四个标志物在第二个验证血清组 n=150 中进行了评估。
TRIM21 在首次验证筛选中的敏感性最高，为 33%，特异性为 100%。将 TRIM21 与 NY-ESO-1、TP53 和 PAX8 结合使用，可提供 67%的敏感性和 94%的特异性，以及 56%的敏感性和 98%的特异性。这四个标志物在第二个验证队列中导致 46%的敏感性和 98%的特异性；TRIM21 的个体敏感性最高，为 36%。
TRIM21、NY-ESO-1 和 TP53 的自身抗体可能与 CA125 一起用于筛查卵巢癌遗传风险女性。
