Biomaker for ovarian and endometrial cancer: hepcidin

Abstract

The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying ovarian cancer status as well as endometrical cancer status in a patient. In particular, it has been found that hepcidin is a biomarker for both ovarian cancer and endometrial cancer and that a panel of biomarkers, including hepcidin, transthyretin and optionally other markers are useful to classify a subject sample as ovarian cancer or non-ovarian cancer. The biomarkers can be detected by SELDI mass spectrometry.

Description

[0001]The present application claims the benefit of U.S. provisional application No. 60 / 662,090 filed Mar. 11, 2005, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The invention relates generally to clinical diagnostics.BACKGROUND OF THE INVENTION[0003]Ovarian cancer is among the most lethal gynecologic malignancies in developed countries. Annually in the United States alone, approximately 23,000 women are diagnosed with the disease and almost 14,000 women die from it. (Jamal, A., et al., CA Cancer J. Clin, 2002; 52:23-47). Despite progress in cancer therapy, ovarian cancer mortality has remained virtually unchanged over the past two decades. (Id.) Given the steep survival gradient relative to the stage at which the disease is diagnosed, early detection remains the most important factor in improving long-term survival of ovarian cancer patients.[0004]The poor prognosis of ovarian cancer diagnosed at late stages, the cost and risk associated wit...

AI Technical Summary

Benefits of technology

[0013]It has further been found that when hepcidin level is used in combination with the level of other biomarkers, the predictive power of the diagnostic test is improved. More specifically, increased levels of hepcidin and decreased levels transthyretin are correlated with ovarian cancer. Increased levels of hepcidin and decreased levels of transthyretin, together with levels of one or more of Apo A1 (decreased level), transferrin (decreased level), CTAP-III (elevated level) and an internal fragment of ITIH4 (elevated level) also are correlated with ovarian cancer. These biomarkers can be further combined with β-2 microglobulin (elevated level), CA125 (elevated level) and / or other known ovarian cancer biomarkers in the diagnostic test.

Problems solved by technology

The poor prognosis of ovarian cancer diagnosed at late stages, the cost and risk associated with confirmatory diagnostic procedures, and its relatively low prevalence in the general population together pose extremely stringent requirements on the sensitivity and specificity of a test for it to be used for screening for ovarian cancer in the general population.

Despite considerable effort directed at early detection, no cost effective screening tests have been developed (Paley P J., Curr Opin Oncol, 2001;13(5):399-402) and women generally present with disseminated disease at diagnosis.

Its use as a population-based screening tool for early detection and diagnosis of ovarian cancer is hindered by its low sensitivity and specificity.

Although pelvic, and more recently, vaginal sonography has been used to screen high-risk patients, neither technique has sufficient sensitivity and specificity to be applied to the general population.

Given the low incidence of ovarian cancer, a screening test intended for the asymptomatic woman with adequate positive predictive remains elusive.

Images