The pancreatic microbiome is associated with carcinogenesis and worse prognosis in males and smokers

• Type of Material: Article
• Authors: Jaideep Chakladar, UC San Diego School of Medicine; Selena Z Kuo, Columbia University; Grant Castaneda, UC San Diego School of Medicine; Wei Tse Li, UC San Diego School of Medicine; Aditi Gnanasekar, UC San Diego School of Medicine; Michael A Yu, Emory University; Eric Y Chang, University of California, San Diego; Xiao Q Wang, Florida State University; Weg M Ongkeko, UC San Diego School of Medicine
• Language: English
• Date: 2020-09-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers12092672
• Title of Journal or Parent Work: Cancers
• Volume: 12
• Issue: 9
• Start Page: 1
• End Page: 15
• Grant/Funding Information: This research was funded by the Academic Senate of the University of California San Diego, grant number RG096651, to W.M.O.
• Keywords: gender; pancreatic adenocarcinoma; tobacco; microbiome; smoking; TCGA
• Research Categories: Health Sciences, Radiology; Health Sciences, Medicine and Surgery

Abstract

An intra-pancreatic microbiota was recently discovered in several prominent studies. Since pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, and the intratumor microbiome was found to be a significant contributor to carcinogenesis in other cancers, this study aims to characterize the PAAD microbiome and elucidate how it may be associated with PAAD prognosis. We further explored the association between the intra-pancreatic microbiome and smoking and gender, which are both risk factors for PAAD. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance, which was correlated to clinical variables and to cancer and immune-associated gene expression, to determine how microbes may contribute to cancer progression. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. This is the first large-scale study to report microbiome-immune correlations in human pancreatic cancer samples. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression.