Dataset Information

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies.

ABSTRACT:

Purpose

Ovarian cancer is a devastating disease and biomarkers for its early diagnosis are urgently required. Serum may be a valuable source of biomarkers that may be revealed by proteomic profiling. Herein, complementary serum protein profiling strategies were employed for discovery of biomarkers that could discriminate cases of malignant and benign ovarian cancer.

Experimental design

Identically collected and processed serum samples from 22 cases of invasive epithelial ovarian cancer, 45 benign ovarian neoplasms, and 64 healthy volunteers were subjected to immunodepletion and protein equalization coupled to 2D-DIGE/MS and multidimensional fractionation coupled to SELDI-TOF profiling with MS/MS for protein identification. Selected candidates were verified by ELISA in samples from malignant (n = 70) and benign (n = 89) cases and combined marker panels tested against serum CA125.

Results

Both profiling platforms were complementary in identifying biomarker candidates, four of which (A1AT, SLPI, APOA4, VDBP) significantly discriminated malignant from benign cases. However, no combination of markers was as good as CA125 for diagnostic accuracy. SLPI was further tested as an early marker using prediagnosis serum samples. While it rose in cases toward diagnosis, it did not discriminate prediagnosis cases from controls.

Conclusions and clinical relevance

The candidate biomarkers warrant further validation in independent sample sets.

SUBMITTER: Timms JF

PROVIDER: S-EPMC4737403 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies.

Timms John F JF Arslan-Low Elif E Kabir Musarat M Worthington Jenny J Camuzeaux Stephane S Sinclair John J Szaub Joanna J Afrough Babak B Podust Vladimir N VN Fourkala Evangelia-Ourania EO Cubizolles Myriam M Kronenberg Florian F Fung Eric T ET Gentry-Maharaj Aleksandra A Menon Usha U Jacobs Ian I

Proteomics. Clinical applications 20141110 11-12

<h4>Purpose</h4>Ovarian cancer is a devastating disease and biomarkers for its early diagnosis are urgently required. Serum may be a valuable source of biomarkers that may be revealed by proteomic profiling. Herein, complementary serum protein profiling strategies were employed for discovery of biomarkers that could discriminate cases of malignant and benign ovarian cancer.<h4>Experimental design</h4>Identically collected and processed serum samples from 22 cases of invasive epithelial ovarian c ...[more]

PMID: 25290619

Similar Datasets

Project description:FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933) and CA-125 (AUC=0.907) were the most informative biomarkers, followed by IL-2 receptor ?, ?1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800). To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912). Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the detection of ovarian cancer.

Dataset Information

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies.

Purpose

Experimental design

Results

Conclusions and clinical relevance

Publications

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets