CNIO study identifies genes linked to pancreatic cancer risk and prognosis

A new study by the National Cancer Research Centre (CNIO) has identified several sets of genes related to the predisposition to develop pancreatic ductal adenocarcinoma (the most common type of pancreatic cancer), as well as the prognosis of the disease once it has appeared.

The study, which has just been published in Nature Communications, represents progress towards the development of screening programmes among the population, an essential tool for advancing early diagnosis. It is led by Núria Malats and Evangelina López de Maturana, from the Epidemiology and Molecular Genetics Group at CNIO.

Early diagnosis poses a major challenge in pancreatic cancer, since high mortality rates are associated with the fact that it is usually detected once it is very advanced.

The genes identified are part of an innate defence mechanism within the body, the complement system. When the proteins of the complement system fail, or if they are lacking or produced in excess, diseases can appear. Very few studies so far have linked the complement system with cancer.

Biomarkers for future screenings

This study, whose first author is Alberto Langtry – currently at Columbia University (USA) after completing his doctoral thesis at CNIO – has discovered that the probability of developing pancreatic cancer may increase when two specific genes in the complement system become mutated.

These genes, called FCN1 and PLAT, could become useful biomarkers for screening high-risk populations. When their presence, along with other factors, indicates susceptibility to pancreatic cancer, the individual may join a monitoring programme.

These are crucial programmes in pancreatic cancer, where high mortality rates are associated with the fact that it is often detected in the very advanced stages. However, first, it is necessary to identify those who are at higher risk of developing this tumour, and in this context, this study is of particular value, as indicated by its authors.

Working towards immunotherapy in pancreatic cancer

Other genes within the complement system are related to two types of immune cells: defenders and regulators. The team has discovered that the activity of certain groups of genes determines the infiltration of defender cells or regulatory cells in the tumour. The former increase cancer survival, while the latter have the opposite effect.

Understanding the relationship between the genes of the complement system and pancreatic cancer may also have implications for treatment. Pancreatic cancer is a 'cold' cancer: it manages to camouflage itself from the immune system, so it is not 'seen' and, therefore, the immune system does not activate to destroy it. That's why pancreatic cancer does not respond to immunotherapy.

This new knowledge about the relationship between the complement system and pancreatic cancer allows us to consider "new immunotherapies targeted at these genes," says Malats.

Funding

The study has been largely financed using public funds provided by the Spanish Health Research Fund (FIS), the Carlos III Health Institute, the Department of Science, Innovation and Universities, and private contributions from the Scientific Foundation of the Spanish Cancer Association (AECC), and the Pancreatic Cancer Collective initiative of the Lustgarten Foundation and Stand Up To Cancer.