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Looking for early detection of pancreatic cancer no matter what stage

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It doesn’t matter how far pancreatic cancer has spread, a new study in the journal Gut says that a certain group of gut microbes can be used to tell if someone is at risk of the disease.

Pancreatic cancer is not one of the most common tumors, but it is one of the most deadly due to its early local extension and metastatic behavior.

A lot of people die from this disease because they don’t know they have it until it’s too late and there aren’t many treatment options.

Researchers from the Spanish National Cancer Research Center (CNIO), led by Nria Malats, and the European Molecular Biology Laboratory (EMBL) in Heidelberg, led by Peer Bork, have discovered a molecular signature of 27 microorganisms in stool samples that could indicate whether patients are at high risk of pancreatic ductal adenocarcinoma, the most common pancreatic cancer, and even diagnose patients with the disease.

Detecting pancreatic cancer early

Pancreatic cancer symptoms are frequently silent and occur in the late stages of the disease, when tumors are usually too large to be removed surgically. As a result, non-invasive, specific, and cheap tests that can diagnose the disease early and enhance patient survival are urgently needed.

“In many cases, once pancreatic cancer is detected, it is too late. We need to diagnose the disease at a much earlier stage, before symptoms appear. To do this, we need to identify and define the population at risk and have good screening tests to detect cancer when it is still curable,” explain the researchers.

Recent research suggests that the microbiome, or the collection of microorganisms that cohabit with cells in the human body, may have a role in the onset and progression of pancreatic ductal adenocarcinoma.

The researchers conducted a unique case-control study with 136 people (57 newly diagnosed patients, 50 healthy controls, and 27 chronic pancreatitis patients) who were thoroughly characterized at epidemiological and clinical levels and from whom saliva, feces, and pancreatic tissue samples were taken to analyze their microbiome. The volunteers came from two Spanish hospitals, one in Madrid (Ramon y Cajal Hospital) and the other in Barcelona (Vall Hebron Hospital).

The most in-depth investigation of the microbiome in pancreatic cancer to date

Contrary to popular perception, it was discovered that while the oral microbiome was not connected with pancreatic cancer, stool bacteria were.

“Sophisticated biostatistical and bioinformatics analyses have allowed us to construct a signature of 27 stool-derived microbes, mostly bacteria, that discriminates very well between cases with pancreatic cancer and controls, both in their most advanced and earliest stages,” adds Malats and Bork.

This gene signature was tested in 5792 faecal metagenomes from 25 research in 18 countries and was validated in an independent investigation conducted in two German centers, Frankfurt (Goethe University Hospital) and Erlangen (University Clinic Erlangen). A Japanese population is now being examined.

Pancreatic cancer, on the other hand, has a complicated aetiology and a number of risk factors, including age, obesity, diabetes, chronic pancreatitis, smoking, excessive alcohol intake, blood type, and a family history of cancer. The scientists accounted for these clinical and demographic variables in the analysis to prevent biases and confirm that the microorganisms discovered are connected with pancreatic cancer and not with obesity, diabetes, or other risk factors.

“This level of analysis is unprecedented in pancreatic cancer metagenome studies,” the investigators add.

The high predictive value of this stool gene profile, according to the researchers in Gut, could serve as a biomarker to classify the population at risk and, if validated in clinical trials, could be employed for early detection of pancreatic cancer.

“Currently, screening programmes are targeted to families with pancreatic cancer aggregation, which represent only 10% of the burden of the disease. The inclusion in these screening programmes of a stool analysis to identify the identified microbial signature could help to detect the rest of the population at risk,” they say.  

Source: 10.1136/gutjnl-2021-324755

Image Credit: CNIO

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