Multiplexed Assay of Serum Biomarkers for Endometrial Cancer
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.
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)
Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
Tarney CM, Wang G, Bateman NW, Conrads KA, Zhou M, Hood BL, Loffredo J, Tian C, Darcy KM, Hamilton CA, Casablanca Y, Lokshin A, Conrads TP, Maxwell GL
Am. J. Obstet. Gynecol. 2019 Nov; Volume 221 (Issue 5): Pages 472.e1-472.e10 PUBMED