Prognostic relevance of extracellular vesicles and circulating nucleic acids in patients undergoing surgery for pancreatic cancer

Poor prognosis of pancreatic cancer is importantly related to the lack of effective treatment strategies and difficulties in diagnosing the disease early. Currently available tumour markers lack sensitivity and specificity to be used for disease detection in asymptomatic patients. Most patients are diagnosed at a late stage and at the time of presentation, only around 20% of patients are eligible for surgical resection. Moreover, despite preoperatively seemingly resectable tumour, unresectable, locally advanced, or even metastatic disease is often discovered upon surgical exploration. Liquid biopsy has become a broadly used clinical approach in various malignancies for molecular profiling of genetic landscapes throughout disease progression. Our research project aims to identify novel non-invasive prognostic and predictive biomarkers in patients with pancreatic cancer undergoing surgery with curative intent. We have designed a longitudinal data and biological sample collection for identification of novel non-invasive biomarkers to assess treatment response and predict clinical outcomes. In the experimental part of our study, we will evaluate microRNAs and/or tumour-specific DNA mutations in plasma and in extracellular vesicles along with other extracellular vesicles’ characteristics as non-invasive prognostic and predictive biomarkers as well as markers of tumour biology. Importantly, extracellular vesicles will be assessed as a distinct source of tumour circulating nucleic acids that may be complementary to other liquid biopsy biomarker sources. Abovementioned biomarkers will be studied 1) in regard to tumour resection to determine their role as a marker of resection radicality; 2) at different time points during follow-up to assess whether they could indicate disease-progression or recurrence; 3) in association with overall survival to define their prognostic and predictive value. Circulating nucleic acids and extracellular vesicles offer great potential to significantly improve clinical decision making in patients with pancreatic cancer. Application of such novel non-invasive blood-based biomarkers for use in clinical practice would allow various treatment modalities to be tailored to each individual patient in regard to tumour characteristics and its prognosis, consequently, leading to improved outcomes and prolonged survival.