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.

Highlights

  • Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer in the world with an annual incidence increased by 2.3 times from 1990 to 2017 [1]

  • The study SRP096338 focuses on the sampling site, which used laser capture microdissection to obtain epithelium and stroma samples from human pancreatic ductal adenocarcinoma frozen sections

  • The samples of the TCGA-PAAD study are labeled with gender and age information. These data will provide us with an effective way to explore the microbial composition of PDAC microenvironments and associations with the abovementioned factors

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer in the world with an annual incidence increased by 2.3 times from 1990 to 2017 [1]. The incidence and mortality of PDAC are nearly equal, with a very poor 5-year survival rate of 9% [2]. Various studies were conducted to dissect the omics landscape to explore mechanisms of carcinogenesis, diagnosis, Microbial Composition of PDAC Tissue and therapy. The kinds of subtypes were revealed by integrated multi-platform analysis, which have prognostic significance and therapeutic implications [3, 4]. There is still no effective molecular markers for early screening, diagnosis, and treatment. A novel approach to PDAC is desperately needed

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