Researchers at the Johns Hopkins Kimmel Cancer Center’s Sol Goldman Pancreatic Cancer Research Center have developed a 3D genomic profiling technique to identify precancerous pancreatic lesions.
Published in Nature, the findings from the study hold the potential to detect pancreatic ductal adenocarcinoma (PDAC) and other types of pancreatic cancer much earlier.
Pancreatic intraepithelial neoplasias (PanINs) are microscopic neoplastic lesions of the pancreas that can progress to invasive PDAC, the most aggressive form of pancreatic cancer, affecting nearly 500,000 people worldwide.
Due to their small size, PanINs are difficult to detect and cannot be identified by standard radiology examination, often meaning that patients diagnosed with cancer have reached an advanced state and metastasised to other organs.
Currently, 2D histological staining methods are used to examine stained tissue under a microscope, providing a limited view of PanINs.
Researchers developed a machine-learning pipeline to analyse and reconstruct thinly sliced and stained tissue from 38 normal pancreatic samples onto hundreds of sequential 2D slides into 3D digital images.
The 3D reconstructions revealed complex networks of interconnected PanINs with an average overall burden of 13 PanINs per cubic centimetre and a range of from one to 31 PanINs per cubic centimetre.
In PDAC patients with cancer in other regions of their pancreas, there was a higher PanIN burden than in those with nonductal disease.
The team further investigated eight of the samples using 3D-guided microdissection and DNA sequencing of specific PanINs, which revealed that the networks were made up of genetically distinct PanINs driven by different gene mutations, including the cancer-causing gene Kirsten rat sarcoma virus (KRAS), which is found in most pancreatic cancers.
Despite not being yet usable in diagnostic settings, CODA can be applied to any tissue, disease or model organism, and researchers aim to continue investigating PanINs in other organ tissues to identify which are clinically relevant to disease.
Laura Wood, associate professor, pathology and oncology, Kimmel Cancer Center and Johns Hopkins University School of Medicine, commented: “One of the ways we can make a difference…with cancer is through prevention and better understanding.
“Now that we know that PanINs are there, we can work on targeting them, such as through KRAS.”