Use of proteomic patterns in serum to identify ovarian cancer.
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.


RESULTS
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).


CONCLUSIONS
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.
Petricoin
Emanuel F
EF
Food 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
Ardekani
Ali M
AM
Hitt
Ben A
BA
Levine
Peter J
PJ
Fusaro
Vincent A
VA
Steinberg
Seth M
SM
Mills
Gordon B
GB
Simone
Charles
C
Fishman
David A
DA
Kohn
Elise C
EC
Liotta
Lance A
LA
D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D011237:Predictive Value of Tests; D020543:Proteome / Q000302:isolation & purification*
D018394:CA-125 Antigen; D020543:Proteome