Overcoming Deficiencies in the Early Detection of Endometrial Cancer: Evaluating Exosomal Proteins as Novel Biomarkers of Disease
Abstract
The proposed research will address the Fiscal Year 2021 Peer Reviewed Cancer Research Program Topic Area of endometrial cancer (EC) and Military Health Focus Area of Gaps in early detection/diagnosis. Rational and Objective: Endometrial cancer is the fourth-most common cancer in women in the United States. Obesity and the associated increase in estrogen levels are associated with the risk of developing type 1 endometrial cancer. The obesity epidemic can be seen impacting all aspects of our health as a country, including our cancer care. Recent clinical evidence has demonstrated an increase in the incidence of EC in young women, likely secondary to the obesity epidemic. Despite the fact that endometrial cancer is on the rise, there are no blood tests that we can currently use to screen for the diagnosis of the disease or to monitor if the disease comes back in those women who has been treated. We aim to address this hole in our screening process for endometrial cancer. Specifically, we want to see if we can identify a cell component called a biomarker. There are a lot of biomarkers available for a variety of diseases, both cancer and not, and therefore we understand the medical utility of having this available for physicians to use. Exosomes are extremely small vesicles which are released by a variety of cells in the body. As opposed to larger cell components that have been previously hypothesized to be useful in cancer identification, exosomes are more specific to the cells of interest (i.e., the cancer cells), and they tend to be more stable and not degrade easily like others. Additionally, because they are extremely small and are less complex than other cell components, we believe that they can be identified as being cancer cell-specific, allowing for better efficacy in screening and maintenance. Problem to be addressed and how it will advance the field: To date, no known biomarkers have proven to be effective for screening or early detection of EC due to the fact that most lack specificity and cannot be obtained using technology that can be relied on for both efficiency and reproducibility. While many protein-based biomarkers have been identified, they have not been confirmed in subsequent studies. This is why exosomal proteins are an attractive source of biomarkers. This work would be the first study exploring the clinical implications of a set of exosomal proteins that we have identified in preliminary studies and plan to expand with further screening of exosomal proteins in multiple sets of patient sample (we will be pulling from three different institution patient sample banks). Our study will addresses these problems by: (1). Determining the exosomal candidate proteins as early biomarkers for EC using multiple and independent set of large cohort sample size; (2). Using a novel technology to isolate exosomes with high purity and yield, and (3). Targeting serum exosomal proteins rather than whole serum or plasma. Therefore, our studies will circumvent the limitations encountered by previous studies and significantly advance our ability to find and validate a biomarker to detect early stage EC. In our pilot studies, this set of candidate proteins (several of which are completely novel) had greater sensitivity and specificity for early-stage EC disease. Potential near-term impacts and translational applicability: The proposed study will achieve with short-term impacts: (i) We have developed a cost-effective medical device that we believe can be moved from use in the lab to use in a clinical setting. In our pilot studies, this instrument yielded high-purity biomarkers in a significantly shorter period of time compared to traditional techniques or currently available medical devices. These factors are critical for moving forward in clinical translation. (ii) We identified candidate exosomal proteins from patient serum samples that are differentially expressed in early-stage EC comp
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210656
Entities
People
- Karuppaiyah Selvendiran
Organizations
- Ohio State University
- United States Army