Identification of novel biomarkers and therapeutic targets in ascites from patients with pancreatic cancer
Pancreatic cancer is a highly lethal disease with a five-year survival rate of <11%. Malignant ascites (MA), the accumulation of fluid in the peritoneal cavity due to cancer, is prevalent in many cancers, including pancreatic. MA worsens symptoms, decreases quality of life, and leads to even poorer prognosis. Current treatments for MA focus solely on the palliation of symptoms, mainly through diuretics and paracenteses. Thus, novel biomarkers and therapeutic targets are urgently needed in order to develop better therapeutic treatments for pancreatic cancer patients with malignant ascites. Extracellular vesicles (EVs) are membrane-bound vesicles produced by cells and released into the extracellular space. EVs carry various bioactive molecules and play a role in cancer development. Because of this, EVs are being actively studied for the diagnosis, prognostication, and surveillance of cancers, pancreatic included. This project aims to utilize single-cell RNA sequencing of MA cells and analysis of EVs using ExoView, proteomics, and RNA sequencing to identify novel biomarkers and therapeutic targets for the treatment of MA in patients with pancreatic cancer. Currently, the protocol for collecting samples has been approved by the institutional review board (IRB) and sample collection is underway. A total of 20 ascites samples will be collected from patients with pancreatic cancer to be analyzed; MA specific biomarkers and potential therapeutic targets will be identified through comparison of MA and benign ascites. Candidate biomarkers and targets will then be further validated in additional samples. If successful, this project could lead to new treatment strategies that significantly improve the outcome of pancreatic cancer patients with MA.