Development of a Multimarker Assay for Early Detection of Ovarian Cancer

Abstract

A B S T R A C T PurposeEarly detection of ovarian cancer has great promise to improve clinical outcome. Patients and MethodsNinety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data. ResultsA training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer. ConclusionA panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.

Pre-Operative Evaluation of Ovarian Tumors by Risk of Malignancy Index, CA125 and Ultrasound

“…Other models of preoperative evaluation should be developed to improve the detection of non-epithelial ovarian cancers, borderline ovarian tumors, and early stage invasive disease (Bast et al, 2005;Yurkovetsky et al, 2010;Li et al, 2013). Ultrasound morphological scoring system should be developed further to improve the detection rate of malignant ovarian tumors (Menon et al, 2010).…”

“…Ultrasound morphological scoring system should be developed further to improve the detection rate of malignant ovarian tumors (Menon et al, 2010). Considering the fact that ovarian cancers are detected mostly at an advanced stage further research and investment is needed in developing a screening tool as the mortality is very high (Bast et al, 2005;Yurkovetsky et al, 2010;Bian et al, 2013;Li et al, 2013).…”

Protein Spectrum Produced by the Dermal Fibroblasts in Children With Crohn’s Disease

“…Сигнатура включает в себя набор качественно или количе-ственно оцениваемых молекулярных параметров, напри-мер генетических полиморфизмов, уровня экспрессии транскриптов, белков, содержания липидов или других метаболитов, измерение которых обеспечивает высокую точность диагностики заболевания [10]. Для получения мультиплексного (многопараметрического) штрих-кода клинического образца могут использоваться различные методы.…”

Biomarkers towards Ovarian Cancer Diagnostics: Present and Future Prospects

“…Besides, it complements serum assays as it was found useful in monitoring the clinical recurrence in cases that showed normal HE4 and CA-125 serum levels. 14 . More recently, a biomarker panel comprising CA-125, HE4, MMP-7, and CA72-4 studied using immunoassays in pretreatment sera from 142 stage I OC cases and 217 healthy controls showed 83.2% sensitivity at 98% specificity 15 .…”