Abstract 6297: New biomarker in liquid biopsies from breast and ovarian cancers

Abstract

Abstract Breast and ovarian cancer (BOC) are among the top ten common cancers in females worldwide and remain important causes of death in women. There are shared risk factors between breast and ovarian cancer such as, BRCA1 and BRCA2. Detecting those risk factors are not enough to detect cancer early as approximately half of breast cancers develop in women who have no identifiable breast cancer risk factor other than gender (female) and age (over 40 years). Identification of specific biomarkers in liquid biopsies is required for early detection of BOC. BOC secretes exosomes in large quantities to blood circulation to communicate with different cell types such as immune cells to support cancer growth and metastasis. We detect a significant and readily measurable expression of a specific peptide from the a2 isoform vacuolar ATPase (a2NTD) in the exosomes isolated from the plasma collected from BOC patients. We found that a2NTD is highly expressed in stage III ovarian cancer. In this stage, the tumor spread outside of the abdomen and/or nearby lymph nodes. a2NTD positively correlates with the CA125 levels in plasma. These data show that plasma a2NTD correlates with tumor cell growth and metastasis. In addition, a2NTD associated breast cancer exosome can contribute to the pathophysiology of the disease as it induces PBMCs to secrete cancer promoting factors such as IL-8, CCL-2, and MMP-9. Importantly, those secreted factors promote angiogenesis and tumor cell migration. a2NTD promotes the immunosuppressive properties of neutrophils by stimulating arginase-1 release. Together, this data shows that a2NTD can be a potential diagnostic biomarker and therapeutic target in breast and ovarian cancer. Citation Format: Safaa A. Ibrahim, Valerie Riehl, Kenneth D. Beaman. New biomarker in liquid biopsies from breast and ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6297.