Molecular Correlates of Venous Thromboembolism (VTE) in Ovarian Cancer

SIMPLE SUMMARY: Ovarian cancer is the most lethal form of gynecologic cancer. The prognosis is worse for patients with ovarian cancer who also develop a blood clot in their legs or lungs, known as a venous thromboembolism (VTE). Between 10-30% of women with ovarian cancer will develop a VTE but the mechanism behind this high incidence is not well understood. The aim of this study was to assess for the presence of tumor-specific molecular markers of VTE in order to better understand the relationship between ovarian cancer and VTE. We performed a comprehensive analysis assessing the proteomic and genomic profiles of 32 patients with ovarian cancer and identified that there are molecular differences in patients with a VTE compared to those without. ABSTRACT: Background: The incidence of venous thromboembolism (VTE) in patients with ovarian cancer is higher than most solid tumors, ranging between 10–30%, and a diagnosis of VTE in this patient population is associated with worse oncologic outcomes. The tumor-specific molecular factors that may lead to the development of VTE are not well understood. Objectives: The aim of this study was to identify molecular features present in ovarian tumors of patients with VTE compared to those without. Methods: We performed a multiplatform omics analysis incorporating RNA and DNA sequencing, quantitative proteomics, as well as immune cell profiling of high-grade serous ovarian carcinoma (HGSC) samples from a cohort of 32 patients with or without VTE. Results: Pathway analyses revealed upregulation of both inflammatory and coagulation pathways in the VTE group. While DNA whole-exome sequencing failed to identify significant coding alterations between the groups, the results of an integrated proteomic and RNA sequencing analysis indicated that there is a relationship between VTE and the expression of platelet-derived growth factor subunit B (PDGFB) and extracellular proteins in tumor cells, namely collagens, that are correlated with the formation of thrombosis. Conclusions: In this comprehensive analysis of HGSC tumor tissues from patients with and without VTE, we identified markers unique to the VTE group that could contribute to development of thrombosis. Our findings provide additional insights into the molecular alterations underlying the development of VTE in ovarian cancer patients and invite further investigation into potential predictive biomarkers of VTE in ovarian cancer.