Abstract 2828: Bacterial diversity correlates with tumor stage and survival in stomach and lung TCGA cancer cohorts
Authors: Rodriguez Rebecca M. , Khadka Vedbar S. , Menor Mark , Deng Youping , Hernandez Brenda Y. 
Published: August 2019

Abstract
Microbiological infections account for up to 20% of the total global cancer burden. Infection-associated cancers are commonly attributed to viral, and to a lesser extent, parasitic and bacterial etiologies. There is growing evidence that microbial variation can influence cancer development, progression, response to therapy, and outcome. We wanted to examine the microbial composition of paired tumor and adjacent normal tissue across various cancer types in order to provide an improved understanding of microbial diversity and abundance patterns of the tumor microenvironment and their influence on clinical presentation and survival. We hypothesized that adjacent normal will be associated with greater species diversity. Methodology: 2234 TCGA tumor & adjacent normal sequencing files (phs000178.v.9.p8; Project ID 14778) representing 1532 cases from stomach adenocarcinoma (TCGA -STAD) and bronchus & lung adenocarcinoma and squamous cell carcinoma (TCGA-LUAD, LUSC ) primary tumor sites were processed through a bioinformatics pipeline designed to generate microbial profiles from raw DNA sequences using PathoScope 2.0 (http://sourceforge.net/projects/pathoscope/) and visualized with KRONA™ plots (Ondov BMC Bioinformatics 2011,12:385). Diversity metrics were calculated to compare taxa between tumor & its paired adjacent normal using vegan R-package (version 2.5.2). Differential abundance was examined using Wilcoxon Signed-Rank Sum test. Bacterial taxa with false discovery rate (FDR) adjusted P-value&lt; 0.05 were considered significantly different at both genus and species level. Results: 509 paired tumor and adjacent normal samples (1:1) were selected for analyses. In stomach we identified 706 distinct bacteria taxa in STAD tumor and adjacent normal while 1004 distinct bacteria taxa were identified in lung cancers tumor and adjacent normal. Average reads ratio per patient was 25% higher in tumor compared to normal adjacent for STAD and 30% lower in tumor compared to normal in lung cancers. Distinct bacterial patterns were observed in tumor versus normal adjacent. In STAD, Helicobacter pylori was significantly less abundant in tumor compared to adjacent normal (log2fc = -4.8, p=&lt;0.0001 FDR= 0.01). None of the taxa detected in lung cancers showed significant differences in abundance in tumor compared to adjacent normal. In lung cancers, relative abundance of certain taxa was associated with tumor stage and years survived (p=&lt;0.001). Alpha diversity varied widely by tumor stage and histology after controlling for age at diagnosis and smoke (p=0.0001). Conclusion: Diversity was correlated to tumor stage and survival. Significant differential abundance was observed for certain taxa for tumor when compared to adjacent normal. Differences in clinical presentation and survival among cancer patients may be explained by microbial abundance patterns.
Citation Format: Rebecca M. Rodriguez, Vedbar S. Khadka, Mark Menor, Youping Deng, Brenda Y. Hernandez. Bacterial diversity correlates with tumor stage and survival in stomach and lung TCGA cancer cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2828.