New genes found that predispose to pancreatic cancer

A new study of National Cancer Research Center (CNIO) has managed to identify several sets of genes related to the predisposition to develop ductal adenocarcinoma of the pancreasthe most common type of pancreatic cancer.

The study, which has just been published in ‘Nature Communications‘, represents a step towards the development of screening programs among the population, an essential tool to advance early diagnosis. The research is led by Núria Malats and Evangelina López de Maturanafrom the Epidemiology and Molecular Genetics Group of the CNIO.

The Center highlights that advancing the diagnosis is an especially important challenge in pancreatic cancer, whose High mortality is associated precisely with the fact that it is usually detected when it is very advanced. The identified genes are part of an innate defense mechanism of the body, the complement system. When proteins in the complement system fail, or are missing or overproduced, diseases can occur. Very few studies so far link the complement system with cancer.

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

These genes, called FCN1 and PLAT, could become useful biomarkers for screening risk populations. When its presence and that of other factors indicate susceptibility to pancreatic cancer, the person could enter follow-up programs.

In this sense, the authors of the study indicate that they are crucial programs in pancreatic cancer, whose high mortality is associated with the fact that it is usually detected in very advanced stages; But first we must identify those who are most at risk of developing this tumor, and in that context this new work takes on special value.

Towards immunotherapy in pancreatic cancer

Other genes in the complement system have to do with two types of immune cells, defenders and regulators. The team has discovered that the activity of certain groups of genes determines whether defense cells, or regulatory cells, infiltrate the tumor. The former increase survival from cancer, while the latter have the opposite effect.

Understanding the relationship of complement system genes to pancreatic cancer may also have implications for treatment. Pancreatic cancer is a cold cancer: it achieves camouflage against the immune system, which therefore does not ‘see’ it and is not activated to destroy it. This is why pancreatic cancer does not respond to immunotherapy.

“The new knowledge about the relationship between the complement system and pancreatic cancer allows us to think about “new immunotherapies targeting these genes,” says Malats.

A website and an app to classify pancreatic cancer

Another challenge of pancreatic cancer is its heterogeneity, the degree of aggressiveness of the tumors is diverse, and also its response to treatments. Several classification models have been proposed, but each one identified different subtypes.

A new work also led by Malats at the CNIO has compiled the information from all these models and, with the help of algorithms, has integrated it into a new consensus classifier. Besides, has developed a website and an application that facilitate its use: RNA from a tumor sample is sequenced, the data is uploaded to the website or app, and the tumor subtype is obtained.

The new classifier establishes two subtypes according to the information of the tumor cells, and another two according to that of the stroma, the group of healthy cells that surrounds the tumor cells and that influences the effectiveness of the treatments. The study is published in ‘Genome Medicine‘and its first author is Pablo Villosladapostdoctoral researcher in the Malats group.

“The new model may indicate that the tumor corresponds to the subtype that reacts best to one of the most common treatments for this cancer. Hence its importance for clinical practice. The classifier also serves to study risk factors for pancreatic cancer,” says Malats.

“We know that tobacco increases the risk, slightly, but consistently. Perhaps what happens is that we have studied it for pancreatic cancer in general, and it turns out that there are subtypes for which the risk increases, and others do not. Now that we are able to separate these subtypes we can verify it,” said the researcher.

The study published in ‘Nature Communications’ It has been financed mainly with public funds from the Health Research Fund (FIS), the Carlos III Health Institute, the Ministry of Science, Innovation and Universities and private contributions from the Scientific Foundation of the Spanish Association against Cancer (AECC), and the Pancreatic Cancer Collective initiative of the Lustgarten Foundation and Stand Up To Cancer.

The work published in ‘Genome Medicine’ has received funding from the Health Research Fund (FIS), the Carlos III Health Institute, the research and innovation (R&I) framework program of the European Union (EU) and the Pancreatic Cancer Collective initiative of the Lustgarten Foundation and Stand Up To Cancer.