Dr Rodrigo Motta

People with PSC are at higher risk of getting bile duct cancer, called cholangiocarcinoma (CCA). Despite lots of promising research in this area, we still don’t have a reliable way to detect or predict who will get it.

In PSC, the body ‘attacks’ the bile ducts (small tubes in the liver), causing inflammation and scarring (‘strictures’) in these tiny tubes. In many people with PSC, we can see these strictures in an MRI of the liver, which we call large duct PSC. The problem is that CCA can look like these strictures and vice versa, making it hard to detect early on. If there is a suspicion of cancer, patients might have to have an endoscopy of the bile ducts which is an invasive procedure.

Recent studies have shown that we can identify changes in the DNA that regulate the production of proteins: these changes are called ‘DNA methylation’. They have been associated with the presence of cancer, how fast the cancer grows and how aggressive it is. Methylation changes can be detected in the blood and bile of people with PSC and may be used to detect cancer at an early stage.

Each of our organs is composed of cells with a protocol (DNA), which they follow to create proteins that are important for our body. All cells have access to the entire protocol but depending on the part of the body, the cells will focus on reading different parts of the protocol that are specific and important to where these cells are.

Triggers, such as smoking, pollutants, harmful microorganisms, inflammation, and scarring, like we see in PSC, create a lot of disruptive noise, also called DNA methylation. The noise can make it difficult for the cells to read the protocol correctly (like when someone spills water on paper and the ink becomes smudgy).

Sometimes, the noise makes the cells misinterpret the protocol and they may produce incorrect amounts of proteins. This might affect the structure or the function of that part of the body. We know, for instance, that some old cells in the bile ducts of people with PSC are affected by this noise. When these cells are damaged, instead of following the normal protocol that would lead to their death and exchange for a new and healthy cell, they try as hard as they can to stay alive and end up producing lots of proteins that cause harm to the other cells around them.

Many patterns of noise are involved in the development of cancers. In fact, the bile in people with bile duct cancer has different patterns of noise compared to people with PSC who don’t have cancer and we can measure these patterns of noise.

This area of medical research is new and is called ‘epigenetics’.

Dr Motta believes that the patterns of noise in the blood and bile of people with PSC could be used to spot early signs of bile duct cancer.