Pancreatic cancer is a common malignancy of the digestive system, of which 80%-90% of patients belong to pancreatic ductal adenocarcinoma (PDAC), as a veritable "king of cancer", pancreatic cancer after diagnosis of five years survival rate is only 8%, and the incidence of this cancer is still rising worldwide.
Pancreatic cancer onset is insidious, not easy to be diagnosed, when the appearance of obvious symptoms, the disease has progressed to the middle and advanced stages, missed the optimal period of surgical resection, and may occur distant metastasis of the tumor, it can be said that the earlier the pancreatic cancer is detected, the greater the likelihood of the patient's survival.
At present, the diagnosis of pancreatic cancer mainly relies on imaging tests, but when the results are interpreted, it is sometimes difficult to distinguish pancreatic cancer from other benign pancreatic diseases. Moreover, in addition to the high-risk population of pancreatic cancer, the average person rarely undergoes pancreatic examination, and there is little chance of early pancreatic cancer being detected through imaging tests.
Obtaining pancreatic cancer-specific markers from blood, urine or feces for screening and early diagnosis of pancreatic cancer is also a good way. Only after so many years, only serum carbohydrate antigen 19-9 (CA19-9) has passed FDA approval and has been applied clinically. However, CA19-9 is more suitable for pancreatic cancer treatment and postoperative recurrence monitoring, and is not very accurate in early diagnosis, and CA19-9 is elevated in the presence of pancreatic disease, biliary tract infection, inflammation, or obstruction.
The peak circuit turns suspicious, the willow dark flower bright and another village, the crowd looks for it thousands of degrees, the clue is in the feces, a recent study published on Gut strongly proves the potential of the fecal microbiome for early screening of pancreatic cancer, combined with CA19-9 detection, but also to make the prediction accuracy to a higher level.
During the initial exploratory phase of the study, a total of 136 volunteers (Spanish cohort) were recruited, including:
There were 57 newly diagnosed, untreated pancreatic cancer patients (25 in the early stages of cancer and 32 in advanced stages of cancer), 29 patients with chronic pancreatitis, and 50 healthy people with age and gender matching.
Considering that some risk factors for pancreatic cancer, such as smoking, alcohol intake, obesity and diabetes, may affect the microbiome in vivo, and with the above factors controlled, the saliva and fecal microbiomes of these volunteers were analyzed through shotgun metagenomic and 16sRNA sequencing, and the researchers found that the fecal microbiome was better able to identify pancreatic cancer patients than the saliva microbiome.
In the fecal microbiome of pancreatic cancer patients, there was a marked increase in the abundance of some strains, including Veillonella atypica, Fusobacterium nucleatum/hwasookii, Alloscardovia omnicolens, while some flora was nearly gone, such as Romboutsia timonensis, Faecalibacterium Prausnitzii (Clostridium prausii), Bacteroides coprocola, Bifidobacterium bifidum (Bifidobacterium), Lacella prasii and decreased abundance of Bifidobacterium are markers of the presence of inflammation in the body.
Based on these fecal flora that differed between cancer patients and non-patients, the researchers constructed a microbiome prediction model (Model-1) to screen out pancreatic cancer patients in the population, and in the Spanish cohort, the accuracy of the model was 0.84 (AUROC=0.5 was equivalent to a random prediction, and AUROC=1 meant that the prediction accuracy was 100%).
Moreover, when the "fecal bacteria cancer test" is combined with the serum CA19-9 "blood cancer test", the prediction accuracy can be improved to AURORAC = 0.94!
What's more, this fecal microbiome change can be detected in both early and advanced pancreatic cancer patients, which means that in the early stages of pancreatic cancer, the fecal microbiome has already changed, and by detecting this change, we can identify those patients who are in the early stages of pancreatic cancer.
The results are encouraging, but "careful verification" is needed – in other samples, is it feasible for the fecal microbiome to predict pancreatic cancer?
The researchers first verified a small range in a German cohort of 76 people, including 44 pancreatic cancer patients and 32 healthy people, the sample treatment was consistent with the Spanish cohort, and the fecal microbiome prediction accuracy AURORAC = 0.83, plus CA19-9, the prediction accuracy AURORAC = 0.91.
Next, in a large database of public gut microbiomes that combined 25 studies with 5792 people with different health conditions involving diseases including chronic pancreatitis, type 1 or type 2 diabetes, colorectal cancer, breast cancer, liver disease, non-alcoholic fatty liver disease, Crohn's disease, and ulcerative colitis, the researchers again validated:
In some patients with liver disease, "fecal bacteria test" occasionally has false positives, which may be due to some similarities in fecal microbiome changes in pancreatic cancer patients and liver disease patients, such as reduced abundance of Shuttlecidium and Bifidobacterium, on the other hand, differences in the treatment of samples in different studies may also lead to false positives (because these false positives were mainly concentrated in two studies).
Of course, the role of the fecal microbiome is not limited to "fecal bacteria to test for cancer", the researchers also found that the microbiome characteristics of tumor tissue in pancreatic cancer patients are similar to those in feces, suggesting that these strains may be involved in the development and progression of pancreatic cancer, "We believe that these strains associated with pancreatic cancer also provide an entry point for disease prevention and treatment interventions." ”
All in all, this study reveals the application value of the fecal microbiome in the early diagnosis of pancreatic cancer, representing another step forward in non-invasive cancer detection, and looking forward to "fecal bacteria cancer testing" becoming a rising star in the field of tumor detection.
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[1] Kartal E, Schmidt TSB, Molina-Montes E, Rodríguez-Perales S, Wirbel J, Maistrenko OM, Akanni WA, Alashkar Alhamwe B, Alves RJ, Carrato A, Erasmus HP, Estudillo L, Finkelmeier F, Fullam A, Glazek AM, Gómez-Rubio P, Hercog R, Jung F, Kandels S, Kersting S, Langheinrich M, Márquez M, Molero X, Orakov A, Van Rossum T, Torres-Ruiz R, Telzerow A, Zych K; MAGIC Study investigators; PanGenEU Study investigators, Benes V, Zeller G, Trebicka J, Real FX, Malats N, Bork P. A faecal microbiota signature with high specificity for pancreatic cancer. Gut. 2022 Mar 8:gutjnl-2021-324755. doi: 10.1136/gutjnl-2021-324755. Epub ahead of print. PMID: 35260444.
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