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Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.


ABSTRACT:

Background

CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.

Methods

Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1-11 samples per participant) that were contributed 0-18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial. Lowess curves were fit to biomarker levels in cancer patients and control subjects separately to summarize mean levels over time. Receiver operating characteristic curves were plotted, and area-under-the curve (AUC) statistics were computed to summarize the discrimination ability of these biomarkers by time before diagnosis.

Results

Smoothed mean concentrations of CA125, HE4, and mesothelin (but not of B7-H4, DcR3, and spondin-2) began to increase (visually) in cancer patients relative to control subjects approximately 3 years before diagnosis but reached detectable elevations only within the final year before diagnosis. In descriptive receiver operating characteristic analyses, the discriminatory power of these biomarkers was limited (AUC statistics range = 0.56-0.75) but showed increasing accuracy with time approaching diagnosis (eg, AUC statistics for CA125 were 0.57, 0.68, and 0.74 for > or = 4, 2-4, and <2 years before diagnosis, respectively).

Conclusion

Serum concentrations of CA125, HE4, and mesothelin may provide evidence of ovarian cancer 3 years before clinical diagnosis, but the likely lead time associated with these markers appears to be less than 1 year.

SUBMITTER: Anderson GL 

PROVIDER: S-EPMC2802285 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.

Anderson Garnet L GL   McIntosh Martin M   Wu Lieling L   Barnett Matt M   Goodman Gary G   Thorpe Jason D JD   Bergan Lindsay L   Thornquist Mark D MD   Scholler Nathalie N   Kim Nam N   O'Briant Kathy K   Drescher Charles C   Urban Nicole N  

Journal of the National Cancer Institute 20091230 1


<h4>Background</h4>CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.<h4>Methods</h4>Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1-11 samples per participant) that were contributed 0-18 years before ova  ...[more]

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