The Landscape of Microbial Composition and Associated Factors in Pancreatic Ductal Adenocarcinoma Using RNA-Seq Data

Abstract

Recent research studies on interrogation of the tumor microbiome (including bacteria, viruses, and fungi) have yielded important insights into the role of microbes in carcinogenesis, therapeutic responses, and resistance. Once thought to be a sterile organ, a number of studies have showed the presence of microbes within this organ in PDAC status. A microbiome–pancreas axis for PDAC (pancreatic ductal adenocarcinoma) carcinogenesis is proposed. However, the microbial composition of localized PDAC tissue is still unclear. The associations between microbiome and PDAC reported in previous studies were detected in an indirect way, which mostly used samples from stool, oral saliva, and intestinal samples. This study integrated 582 samples derived from PDAC tissues across four datasets and presented a landscape of tumor microbiome at the genus level in PDAC based on remining of RNA-Seq data. On average, there are hundreds of genera distributed in the PDAC tissue, and dozens of core microbiota were identified by PDAC tissue. The pan-microbiome of PDAC tissue was also estimated, which might surpass 2,500 genera. In addition, sampling sites (stroma vs. epithelium) and tissue source (human tissue vs. PDX) were found to have great effects on the microbial composition of PDAC tissue, but not the traditional risk factors (sex and age). It is the first study to systematically focus on exploring the microbial composition of PDAC tissue and is helpful to have a deep understanding of tumor microbiome. The identified specific taxa might be potential biomarkers for follow-up research studies.

The Role of Microbiota in Pancreatic Cancer

“…Fluorescence in situ hybridization, applied to tumor-associated microbiota, recorded a decreased abundance of Lactobacillus spp. and an increased abundance of Fusobacterium spp., Malassezia spp., and Firmicutes [ 4 , 6 , 18 , 23 , 45 , 49 , 50 ]. Several species were linked to PC microbiota, an emblematic example of which is Helicobacter (H.) pylori , which nevertheless exhibits controversial properties.…”

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

“…Differential microbiota profiles have been detected in the oral cavity, in the pancreas, and in the gut through the analysis of saliva, tumor tissue, pancreatic juice, pancreatic cyst fluid, and stool samples of pancreatic cancer patients [ 111 ]. These were, amongst others, increased abundancies of Porphyromonas gingivalis , Graniculatella gingivalis , Fusobacterium [ 111 , 112 , 113 ] and decreased abundancies of Neisseria elongata and Streptococcus mitis [ 113 ] in the oral cavity, increased abundance of Fusobacterium spp., Malassezia spp., Firmicutes and Proteobacteria [ 114 , 115 , 116 , 117 , 118 ], and decreased abundance of Lactobacillus in the pancreas [ 114 ], increased abundance of Gammaproteobacteria [ 119 ], Helicobacter pylori , Porphyromonas , Prevotella , Bifidobacterium , Synergistetes [ 114 , 120 , 121 ] and decreased abundance of beneficial probiotics and butyrate-producing bacteria in the gut [ 119 , 122 ].…”