Abstract 6097: Alterations of the pancreatic tumor microbiome: the role of biliary stents

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers, with an average five-year survival of 9% across all stages. This dismal prognosis can be attributed to advanced stage at diagnosis and poorly effective treatment options. Growing evidence has shown that commensal microbiota play a pivotal role in the oncogenicity of a number of malignancies. Traditionally, the pancreas has been considered to be a sterile organ, with an environment that could not promote microbial colonization. However, advances in metagenomics and next-generation sequencing have enabled researchers to identify that bacterial DNA can be detected in PDAC tissue. Moreover, Geller et al. showed that presence of intratumor Gammaproteobacteria conferred resistance to the chemotherapy agent gemcitabine, further emphasizing the importance of understanding the role of these microbiota. Bacterial colonization of the pancreas in PDAC is thought to be due to migration of intestinal microbiota that thrive in the pancreatic tumor microenvironment, however there is still much unknown about the factors that promote growth of these bacteria. It is imperative to address these gaps in knowledge to enhance the efficacy of anti-tumor drug therapies. We hypothesized that biliary stent placement contributes to the increased abundance of bacterial signatures seen in PDAC. We obtained matched tumor and normal pancreatic tissue specimens from 27 patients who had undergone surgical resection for PDAC from the University of Minnesota biorepository. DNA extraction of these tissue specimens was performed with DNeasy PowerSoil Kit (Qiagen) in accordance to manufacturer instructions. Out of the 27 patients examined, microbial abundance was detected in samples from 18 patients (67%) via qPCR targeting the 16S rRNA gene. The V4 hypervariable region of the 16S rRNA gene was then amplified and pair-ended sequenced on the Illumina MiSeq platform by the University of Minnesota Genomics Core. We found that 26 (48.1%) out of 54 pancreatic tissue samples harbored detectable bacterial communities. This comprised of 13 (50%) healthy and 13 (50%) neoplastic tissue samples. The most abundant families of bacteria included Ruminococcaceae, Enterobacteriaceae, and Staphylococcaceae. Bacterial DNA was identified in 19 (73%) samples from patients with biliary stents and 7 (27%) samples from patients without biliary stents. Our results confirmed that microbial signatures were more detectable in patients who had undergone biliary stent placement (χ2 = 7.21, p = 0.007). This finding suggests that biliary stents lead to specific alterations in pancreatic microbial floral in the setting of PDAC that encourage bacterial growth. Further studies addressing whether these compositional alterations could contribute to increased chemoresistance will be essential for optimizing medical therapies in the future. Citation Format: Harika Nalluri, Christopher Staley, Eric H. Jensen. Alterations of the pancreatic tumor microbiome: the role of biliary stents [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6097.