Spanish scientists have identified genes that help identify a person’s risk of developing pancreatic cancer – as well as its likely prognosis.
The disease is one of the deadliest due its difficulty to detect, which often results in it being found at a very advanced stage.
The findings by the Centro Nacional de Investigaciones Oncologicas (CNIO) focus on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer.
The research could help identify individuals who may benefit from early detection programmes.
Details of the study have been published in the journal Nature Communications and were led by researchers Nuria Malats and Evangelina Lopez de Maturana from CNIO’s Epidemiology and Molecular Genetics Group.
The genes identified are part of the body’s innate defence system, known as the complement system. This system plays a key role in immune responses, and when its proteins fail, are missing or are produced in excess, disease can develop.
According to CNIO, very few studies to date have linked the complement system to cancer.
The research shows that the likelihood of developing pancreatic cancer increases when two specific complement system genes – FCN1 and PLAT – are mutated.
These genes could become useful biomarkers for screening people at higher risk. When their presence, combined with other factors, suggests susceptibility to pancreatic cancer, patients could be enrolled in monitoring and follow-up programmes.
The team also found that other complement system genes are associated with two types of immune cells: protective cells and regulatory cells.
Their analysis shows that the activity of certain gene groups determines whether tumours are infiltrated by protective immune cells, which improve survival, or regulatory cells, which have the opposite effect.
Understanding how the complement system is linked to pancreatic cancer may also open new treatment pathways.
As Malats explains, pancreatic cancer is considered a ‘cold’ tumour because it is able to evade the immune system, preventing an effective immune response.
This is one of the reasons why pancreatic cancer does not currently respond well to immunotherapy. The new findings, she says, ‘allow us to consider new immunotherapies targeted at these genes’.
The team has also developed a freely accessible website and app to support its use.
By sequencing the RNA of a tumour sample and uploading the data, clinicians can determine the tumour subtype.
The classifier identifies two subtypes based on tumour cell information and two based on the surrounding stroma – the healthy tissue that influences treatment effectiveness.
The model can indicate which subtype is more likely to respond to commonly used therapies and can also be used to study pancreatic cancer risk factors.
