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

Anderson GL, McIntosh M, Wu L, Barnett M, Goodman G, Thorpe JD, Bergan L, Thornquist MD, Scholler N, Kim N, O'Briant K, Drescher C, Urban N - J. Natl. Cancer Inst. (2009)

Bottom Line: Except for CA125, their behavior in the prediagnostic period has not been evaluated.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.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, PO Box 19024, M3-A410, Seattle, WA 98109-1024, USA. garnet@whi.org

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.

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Related in: MedlinePlus

Lowess curves of standardized marker levels by time before diagnosis or reference date. Standardized marker levels were rescaled to have a mean of 0 and a SD of 1 among control subjects. A) CA125. One cancer patient and one control subject had standardized CA125 levels that were greater than 6 and so were excluded from the graph. B) Human epididymis protein 4. C) Mesothelin. D) B7-H4. E) Decoy receptor 3. F) Spondin-2. Dx = diagnosis.
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fig2: Lowess curves of standardized marker levels by time before diagnosis or reference date. Standardized marker levels were rescaled to have a mean of 0 and a SD of 1 among control subjects. A) CA125. One cancer patient and one control subject had standardized CA125 levels that were greater than 6 and so were excluded from the graph. B) Human epididymis protein 4. C) Mesothelin. D) B7-H4. E) Decoy receptor 3. F) Spondin-2. Dx = diagnosis.

Mentions: Similar CA125 protein levels were observed between cancer patients and control subjects until approximately 3 years before diagnosis of ovarian cancer, at which point (by visual inspection), the mean marker level among cancer patients began to rise (Figure 2, A). A similar pattern, though less pronounced, was observed for HE4 protein levels and to a lesser extent, for mesothelin protein levels (Figure 2, B and C). Levels of B7-H4 and DcR3 in cancer patients and control subjects were indistinguishable throughout the study (Figure 2, D and E). Spondin-2 levels showed a slight increase over time among cancer patients resulting in a small separation during the final year before diagnosis (Figure 2, F).


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

Anderson GL, McIntosh M, Wu L, Barnett M, Goodman G, Thorpe JD, Bergan L, Thornquist MD, Scholler N, Kim N, O'Briant K, Drescher C, Urban N - J. Natl. Cancer Inst. (2009)

Lowess curves of standardized marker levels by time before diagnosis or reference date. Standardized marker levels were rescaled to have a mean of 0 and a SD of 1 among control subjects. A) CA125. One cancer patient and one control subject had standardized CA125 levels that were greater than 6 and so were excluded from the graph. B) Human epididymis protein 4. C) Mesothelin. D) B7-H4. E) Decoy receptor 3. F) Spondin-2. Dx = diagnosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2802285&req=5

fig2: Lowess curves of standardized marker levels by time before diagnosis or reference date. Standardized marker levels were rescaled to have a mean of 0 and a SD of 1 among control subjects. A) CA125. One cancer patient and one control subject had standardized CA125 levels that were greater than 6 and so were excluded from the graph. B) Human epididymis protein 4. C) Mesothelin. D) B7-H4. E) Decoy receptor 3. F) Spondin-2. Dx = diagnosis.
Mentions: Similar CA125 protein levels were observed between cancer patients and control subjects until approximately 3 years before diagnosis of ovarian cancer, at which point (by visual inspection), the mean marker level among cancer patients began to rise (Figure 2, A). A similar pattern, though less pronounced, was observed for HE4 protein levels and to a lesser extent, for mesothelin protein levels (Figure 2, B and C). Levels of B7-H4 and DcR3 in cancer patients and control subjects were indistinguishable throughout the study (Figure 2, D and E). Spondin-2 levels showed a slight increase over time among cancer patients resulting in a small separation during the final year before diagnosis (Figure 2, F).

Bottom Line: Except for CA125, their behavior in the prediagnostic period has not been evaluated.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.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, PO Box 19024, M3-A410, Seattle, WA 98109-1024, USA. garnet@whi.org

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.

Show MeSH
Related in: MedlinePlus