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Use of proteomic patterns in serum to identify ovarian cancer
Emanuel F Petricoin1, Ali M Ardekani, Ben A Hitt
1Food and Drug Administration/National Institutes of Health Clinical Proteomics Program, Department of Therapeutic Proteins/Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. petricoin@cber.fda.gov
Background:
New technologies for the detection of early-stage ovarian cancer are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. We developed a bioinformatics tool and used it to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the ovary.
Methods:
Proteomic spectra were generated by mass spectroscopy (surface-enhanced laser desorption and ionisation). A preliminary "training" set of spectra derived from analysis of serum from 50 unaffected women and 50 patients with ovarian cancer were analysed by an iterative searching algorithm that identified a proteomic pattern that completely discriminated cancer from non-cancer. The discovered pattern was then used to classify an independent set of 116 masked serum samples: 50 from women with ovarian cancer, and 66 from unaffected women or those with non-malignant disorders.
Findings:
The algorithm identified a cluster pattern that, in the training set, completely segregated cancer from non-cancer. The discriminatory pattern correctly identified all 50 ovarian cancer cases in the masked set, including all 18 stage I cases. Of the 66 cases of non-malignant disease, 63 were recognised as not cancer. This result yielded a sensitivity of 100% (95% CI 93--100), specificity of 95% (87--99), and positive predictive value of 94% (84--99).
Interpretation:
These findings justify a prospective population-based assessment of proteomic pattern technology as a screening tool for all stages of ovarian cancer in high-risk and general populations.
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