Microbiota and Metabolites Alterations in Pancreatic Head and Body/Tail Cancer Patients

Pancreatic ductal adenocarcinoma (PDAC) can be divided into pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) according to the anatomical position of tumors. There is increasing evidence that tumors at different sites exhibit different genetic or molecular features and clinical manifestations, and can affect the survival and outcomes of PDAC patients. Studies have shown that the prognosis of PBTC is worse than that of PHC, which is partly attributed to the relatively late clinical presentation of PBTC patients and the lack of overt symptoms such as obstructive jaundice, which is common in PHC. However, it has also been shown that the worse survival of PBTC compared to PHC is not related to the disease stage. Previous studies have investigated the molecular differences between PHC and PBTC and found that the frequency of SMAD4 mutation in PBTC was significantly higher than that in PHC at early stages (I-II). In the late stage (III-IV), PBTC had higher mutation frequency of Kirsten rat sarcoma viral oncogene homolog (KRAS) and mitogen-activated protein kinase (MAPK) pathway, but lower frequency of genomic alterations which can be targeted by drugs. The above genetic and molecular differences may be related to the clinical differences between PHC and PBTC.

However, the differences in microbial composition and metabolism between PHC and PBTC have not been fully studied and discussed, and their relationship with clinical manifestations and prognosis is also unclear. In this study, the investigators aimed to analyze the microbial and metabolic differences between PHC and PBTC through 16S ribosomal ribonucleic acid (rRNA) sequencing and untargeted metabolome analysis to further explore the etiology and pathogenesis of PDAC at different anatomical positions.