Identification of an Immune/Methylation Signature Predicting for Recurrence in Early Stage Ovarian Cancer
Abstract
The survival of women with high-grade epithelial ovarian cancer is directly related to the spread of the tumor. Women with disease limited to the pelvis do well, with many being cured, while those patients whose tumor has spread outside of the pelvis suffer recurrences, and the majority will die from the disease. Nevertheless, the standard of care for patients with high-grade ovarian cancer is surgery followed by six cycles of chemotherapy (carboplatin/taxol), regardless of the spread of the tumor. Although some early-stage patients are benefiting from this strategy, approximately 50-60% of patients with high-grade early-stage cancer will not develop recurrent disease, even in the absence of chemotherapy. These patients thereby suffer unnecessary short- and long-term toxicities from chemotherapy with no benefit. Thus, the development of accurate biomarkers predictive of tumor recurrence becomes essential to identify women with early-stage disease who will benefit from chemotherapy while sparing the rest the unnecessary treatment with quality-of-life and cost-effectiveness ramifications. This approach parallels efforts in breast cancer where tests like “oncotype dx” provide valuable information on disease recurrence to women with early-stage breast cancer. To the best of our knowledge, there is no available large-scale molecular characterization of early-stage ovarian tumors. With funding from the Department of Defense, we have established a multi-institutional consortium through which we have collected 400 early-stage ovarian cancer specimens with complete clinical annotation. We have previously determined all of the genes that are found to be either amplified or deleted and over-expressed in these specimens through DOD funded projects. This project will build on the previous analysis by now identifying the genes that are methylated and determining the immune infiltration within these specimens. Methylation is a modification of DNA that can alter the expression of genes and have a major effect on cancer growth and clinical behavior. By characterizing the patterns of modification of DNA and the number and nature of immune cells that are found in the tumors, we will be able to identify novel therapeutic biomarkers and design stratification of early-stage ovarian cancer patients who are most likely to benefit from targeted interventions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910192
Entities
People
- Michael Birrer
Organizations
- United States Army
- University of Alabama at Birmingham