Researchers highlight 27 microorganisms in stool that suggest pancreatic ductal adenocarcinoma, a common pancreatic cancer that could be used for early detection.
“In many cases, once pancreatic cancer is detected, it is too late,” explains the research team, made up of researchers from the Spanish National Cancer Research Centre (CNIO), led by Núria Malats, and the European Molecular Biology Laboratory (EMBL) in Heidelberg, steered by Peer Bork.
“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 the cancer when it is still curable,” the team points out.
Using patient samples provided by clinical collaborators, the team applied a shotgun metagenomic approach, also using 16S rRNA amplicon sequencing to the samples.
The samples originated from a Spanish case–control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case–control study (n=76), in the validation phase.
The samples were also characterised at epidemiological and clinical levels, where saliva, faeces and pancreatic tissue were taken to analyse their microbiome.
Findings revealed the oral microbiome was not associated with pancreatic cancer, but faecal microbes 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,” says Malats and Bork.
Additional validation of the gene signature was achieved via an independent study carried out at the Goethe University Hospital and University Clinic in Erlangen and in 5,792 faecal metagenomes from 25 studies in 18 countries. The signature is currently being studied in a Japanese population.
To avoid biases and to ensure the microbes identified are associated with pancreatic cancer and not with obesity, diabetes, or other risk factors, the authors controlled for these clinical and demographic variables in the analysis.
“This level of analysis is unprecedented in pancreatic cancer metagenome studies,” the team adds.
The team go onto discuss the importance of the high predictive value of the stool gene signature and its possibilities of serving as a biomarker to define the population at risk
According to the researchers, if validated in clinical trials, it could be used for early diagnosis 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 team write in the journal Gut.
“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 add.
Published online: doi.org/10.1136/gutjnl-2021-324755
“A faecal microbiota signature with high specificity for pancreatic cancer”
Authors: Ece Kartal et al