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Principal Investigator
Name
Anna Lokshin
Degrees
-
Institution
University of Pittsburgh
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2006-0288
Initial CDAS Request Approval
Nov 21, 2006
Title
Multiplexed Assay of Serum Biomarkers for Endometrial Cancer
Summary
Endometrial carcinoma is the most common gynecologic cancer. Despite the advances that have been made in other cancers, both the annual incidence of and the death rate associated with endometrial cancer appear to be rising. Lack of screening test for this type of cancer is associated with excess mortality for women who do not present with vaginal bleeding and other early warning signs for endometrial cancer. Although the prognosis for endometrial cancer is generally good, cancers identified at later stages are associated with high levels of morbidity and mortality. Therefore, prevention and early detection represent our best hope to overcome this disease. We hypothesize that a multi-marker panel would provide the requisite high sensitivity and specificity for early detection of endometrial cancer, to be utilized for screening of target populations. We have identified a biomarker panel that discriminated endometrial cancer cases from healthy controls with a sensitivity of greater than 99% at a specificity of 99% in a case/control cross-validation set. The objective of this study is to develop a reliable serum-based assay for early detection of endometrial cancer based on the longitudinal patterns of multiple biomarkers. To achieve this objective, the following Specific Aims are proposed: 1. Validate the optimized biomarker panels in independent blinded case/control setting; 2. Validate these panels in a retrospective longitudinal study (PLCO). Use 100 ml of sera from 100 participants who subsequently developed endometrial cancer and 100 ml sera from 3 matched controls who did not develop endometrial cancer per case of endometrial cancer.
Aims

We hypothesize that a multi-marker panel would provide the requisite high sensitivity and specificity for early detection of endometrial cancer, to be utilized for screening of target populations. We have identified a biomarker panel that discriminated endometrial cancer cases from healthy controls with a sensitivity of greater than 99% at a specificity of 99% in a case/control cross-validation set. The objective of this study is to develop a reliable serum-based assay for early detection of endometrial cancer based on the longitudinal patterns of multiple biomarkers. To achieve this objective, the following Specific Aims are proposed: 1. Validate the optimized biomarker panels in independent blinded case/control setting. In Aim 1, we propose to validate the 8-biomarker panel (Preliminary Data and Aim 1) in an independent blinded case/control set of serum samples (endometrial cancer, non-cancerous endometrial pathology, and healthy controls) obtained from Gynecologic Oncology Group (GOG) Repository (Columbus, OH) thereby completing the required Phase II Case/Control validation step in accordance with EDRN guidelines. 2. Validate these panels in a retrospective longitudinal study (PLCO). Use 100 ml of sera from 100 participants who subsequently developed endometrial cancer and 100 ml sera from 3 matched controls who did not develop endometrial cancer per case of endometrial cancer. We will perform Phase III validation of the 8-biomarker panel in retrospectively collected prospective study, PLCO samples of participants who developed endometrial cancer or remained healthy. To accomplish this Aim, we will (i) develop a bioinformatics algorithm for screening positivity in retrospective longitudinal study based on combinations of markers; (ii) validate performance of diagnostic multimarker panels in retrospective longitudinal study in postmenopausal women, determine sensitivity, specificity, positive predictive value; (iv) evaluate, as a function of time before clinical diagnosis, the capacity of biomarker panels to detect preclinical disease; (iii) determine a screening interval for future prospective studies.

Collaborators

Alex Lisovich (University of Pittsburgh)
Larry Maxwell (Walter Reed Army Medical Center)
Karen Lu (MD Anderson Cancer Center)
Anna Lokshin (University of Pittsburgh)
Zoya Yurkovetsky (University of Pittsburgh)

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