The accuracy of the combined test was then equal to 0.94 of the area under the receiver operating characteristic curve (AUROC).1 This result was confirmed with an independent German PDAC cohort (0.83 AUROC). In addition, the PDAC-related specificity was confirmed against 25 publicly available metagenome studies with a total of 5,792 participants suffering from a variety of other diseases. In the opinion of the scientists involved, the procedure could thus represent a non-invasive, cost-effective and reliable method for screening for PDAC.
Pancreatic carcinoma continues to be one of the tumours with the worst prognosis. The main reason is that there is still no suitable early detection method that is adequate for monitoring larger populations or even just risk groups.
Pancreatic tumours are often first discovered in advanced stages that render curative treatment impossible. Around 19,000 new cases occur in Germany every year. The 5-year survival rate for both sexes is a sobering 10%, with more than 60% of those affected dying during the first year of the disease. The vast majority of pancreatic cancers are of the PDAC type. Risk factors include age, smoking and alcohol consumption, as well as various pre-existing conditions such as chronic pancreatitis, diabetes mellitus, obesity and asthma.2
Given this situation, it is easy to understand why a reliable screening parameter for the disease is of the utmost urgency. However, it was by no means obvious that the intestinal microbiome of all factors would play a decisive role in this. Up until now, the search for suitable screening parameters has included urine and serum factors as well as tissue samples of the organ. Nevertheless, only CA 19-9 and, with some limitations, the carcinoembryonic antigen (CEA) have been established as rather weakly correlated indicators of pancreatic carcinoma. Links to the mouth and gut microbiome have also been established by 16S rRNA analysis, but have not yet been evaluated for their potential for screening, according to the authors of the study.
The scientists headed by Ece Kartal from the European Molecular Biology Laboratory in Heidelberg have now examined a Spanish PDAC cohort of 57 participants as part of their case-control study and compared their microbiome with that of 50 control subjects and 29 patients with chronic pancreatitis. The analysis was not limited to the 16S rRNA method, but also included the more extensive so-called shotgun metagenomics and fluorescence in situ hybridisation (FISH). Samples were taken from the microbiome of saliva, the intestine and from carcinogenic and healthy pancreatic tissue.
The evaluation revealed the best predictive power for a group of 27 faecal species that were targeted and quantified. In the process, the team also confirmed earlier indications of an independent pancreatic microbiome.
The authors now speculate that a more detailed investigation of the distinctive species could also provide clues to potential future prevention and treatment strategies in PDAC. Either way, the discovery of an inexpensive and simple screening procedure marks a breakthrough in the diagnosis of PDAC, which gives hope of leading to decisive improvements in the prognosis of the disease in the near future.
Sources:
1. Kartal E, et al. A faecal microbiota signature with high specificity for pancreatic cancer. Gut 2022; 0: 1–14.
2. Zentrum für Krebsregisterdaten.