Use of proteomic patterns in serum to identify ovarian cancer

EF Petricoin, AM Ardekani, BA Hitt, PJ Levine… - The lancet, 2002 - thelancet.com
EF Petricoin, AM Ardekani, BA Hitt, PJ Levine, VA Fusaro, SM Steinberg, GB Mills, C Simone
The lancet, 2002thelancet.com
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 …
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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