Association between intra-tumoral microbiome and genetic alterations in intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND/OBJECTIVES: We previously demonstrated that intra-tumoral microbiome infection may affects the clinicopathological characteristics of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and showed that these characteristics are also influenced by gene mutations. The aim of this study was to investigate whether specific microbiome infections lead to alterations in the expression of specific genes in IPMNs.

METHODS: DNA was extracted from 26 resected IPMN samples and subjected to genetic mutation assessment and microbiome analysis. The relationship between intra-tumoral microbiome and genetic alterations was investigated.

RESULTS: There was an increasing trend in the percentage of Firmicutes in KRAS- and GNAS-mutated IPMNs, whereas Proteobacteria tended to decrease in KRAS-mutated IPMNs. KLF4-mutated IPMNs, particularly within the KRAS-mutated group, had significantly low α-diversity (p < 0.05). The relative abundance of Firmicutes and Proteobacteria was significantly higher in KLF4-mutated IPMNs, especially in KLF4-mutated IPMNs among the KRAS-mutated groups. An increased relative abundance of Firmicutes and Proteobacteria, along with the associated reduction in microbial diversity, was associated with a higher frequency of gene mutations, including KLF4.

CONCLUSIONS: This study suggest that the intratumoral microbiome may be linked to the genetic characteristics of IPMNs and potentially contribute to their malignant progression.