Cell-Free Transcriptome Profiling for Detection and Treatment Monitoring of Liver Cancer
Abstract
This proposal addresses the call for the Fiscal Year 2020 Peer Reviewed Cancer Research Program Idea Award in the area of liver cancer. Hepatocellular carcinoma (HCC), the most common form of liver cancer, is rapidly increasing in incidence in the United States and is the fourth leading cause of cancer mortality worldwide. Most patients present with unresectable disease, and locoregional and systemic therapies have poor response rates, with frequent disease recurrence. Currently, only 2.4% of metastatic liver cancer patients survive more than 5 years. Early detection of HCC could significantly improve 5-year survival rates through potentially curative therapies, including transplant, resection, or ablation. Furthermore, early detection of disease recurrence would enable improved secondary therapies at earlier stages and could improve patient selection by identifying those most likely to benefit from existing therapies. At present, there are no serum biomarkers with the required high sensitivity and specificity needed for early detection of HCC. We hypothesize that molecular signals from a developing tumor and the surrounding microenvironment will be detectible in serum. These biomarkers will represent a highly sensitive and specific technology to detect HCC and will additionally enable robust monitoring of response to treatment. We plan to analyze plasma cell-free RNA (cfRNA) to sequence unique signatures of the tumor and microenvironment. Plasma cell-free RNA can be detectable not only from blood cells, but also from distant tissues, including tumors. In this proposal, we will develop and implement the cfRNA approach to identify accurate diagnostic biomarkers and prognostic indicators of circulating molecular analytes associated with HCC development and its response and evolution to treatment. We will achieve this goal through two specific aims. Specific Aim 1: Develop multi-module transcriptomic analysis of plasma cfRNA to detect cirrhosis, a pre-cancerous condition of HCC, and to differentiate HCC from the cirrhotic population. Specific Aim 2: Pattern the dynamic molecular signature of the cfRNA in HCC patients before and after locoregional treatments and identify the cfRNA predictors of treatment response. Ultimately, we aim to fill a significant gap in early detection and prognosis of HCC, which imposes a substantial health burden on military Service Members, their families, Veterans, and public health in the United States and globally. In addition, development of this technology could enable expansion to other cancers and diseases afflicting United States military personnel and the population at large.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110853
Entities
People
- Thuy Ngo
Organizations
- Oregon Health & Science University
- United States Army