Abstract
BackgroundOver 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.MethodsIn the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n = 106), endometrial cancer (n = 74), benign ovarian tumors (n = 150) and healthy population controls (n = 399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n = 280), endometrial cancer (n = 228), women with benign ovarian tumors (n = 76) and healthy controls (n = 57).ResultsIn the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III–IV with a sensitivity of 0.88 and specificity of 0.92 (AUC = 0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p = 9.56e−22). Also, population controls could be distinguished from ovarian cancer stage III–IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC = 0.89).ConclusionThe PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.FundingThe Swedish Cancer Foundation, Vinnova (SWELIFE), The Foundation for Strategic Research (SSF), Assar Gabrielsson Foundation.
Highlights
In 2012 more than 500,000 women worldwide were diagnosed with epithelial ovarian cancer (OC) or endometrial cancer (EC) [1]
Use of Risk of Ovarian Cancer Algorithm (ROCA) followed by transvaginal ultrasound (TVU) has been shown to result in an increase in the number of women with OCs detected than using of a fixed cutoff for CA125, with half of these women detected by ROCA prior to CA125 > 35 and the other half at the same time as CA125 > 35 [6]
EC is diagnosed at a higher age than OC, which is reflected in the age difference seen between women with EC and those with benign tumors (Table 1)
Summary
In 2012 more than 500,000 women worldwide were diagnosed with epithelial ovarian cancer (OC) or endometrial cancer (EC) [1]. The Risk of Ovarian Cancer Algorithm (ROCA) estimates the changes in annual CA125 measurements to identify women with high-risk scores in a screening population and refer these to specialized units for TVU examination. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) has reported a reduction in ovarian cancer deaths, excluding prevalent cases, using annual screening using ROCA followed by TVU for ROCA positive subjects [7]. Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening
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