Ex vivo spectroscopic characterisation of the biological activity of pancreatic cyst fluid

Abstract

Pancreatic cystic lesions (PCLs) are fluid-filled sacs often identified incidentally during abdominal imaging for unrelated pancreatic indications. While most PCLs are non-cancerous (benign) with no potential progression to pancreatic cancer (PC), some PCLs may undergo malignant transformation and are therefore more likely to progress into invasive cancer. The main challenge lies in separating PCLs that are entirely benign from those that are premalignant, as imaging tools and clinical guidelines remain inadequate. Understanding how these PCLs arise and develop is crucial for the proper management of patients with these lesions. Well-established PDAC cell lines and pancreatic cyst fluid (PCF), the fluid contained within PCLs, represent an invaluable tool for investigating the biological processes driving PCL formation and their eventual malignant transformation. Such information could greatly improve patient risk stratification, as well as avoid unnecessary follow-up and treatment for those who do not need it. Novel approaches based on vibrational spectroscopy may represent a useful adjunct to clinical tests of this sample type, offering a mode for objective assessment as well as providing potential in vivo applications. In the present ex vivo investigation, the first of its kind in this field, a focus was brought to developing a cell line-based model with vibrational spectroscopy for discriminating the response of PDAC cell lines to exposure to PCF. We demonstrate that this approach provides a robust assay which may have potential, with further development, to provide models which are predictive of the trajectory of disease progression in precision medicine.