Abstract 6103: Absence of Mitsuokella multacida is associated with early onset of colorectal cancer
Authors: Amr Elkholy, Michael Behring, Mohammed Mohsen, Prachi Bajpai, Amira Embaby, Doaa Header, Reham Abo Elwafa, Hesham Saeed, Mona Fouad, Waleed Arafat, Upender Manne
Journal: Cancer Research (2020)

Abstract Colorectal cancer (CRC) is a global burden, with an expected 2.2 million annual cases and 1.1 million deaths by 2030. Nearly 90% of CRC cases occur in people over the age of 50. However, early onset (&amp;lt;50 years) of CRC is increasing in Egypt. Prior studies suggest that alteration in microbiome composition (dysbiosis) disturbs the symbiotic relationship between the colorectum and resident micro-organisms and promotes CRC. We hypothesize that, for Egyptians, microbiome dysbiosis is responsible for early-onset of CRC. We further hypothesize that there is cross-talk between the microbiome, tumor molecular features, and the immune microenvironment. Thus, we investigated the molecular profiling of these patients via integrated transcriptional-microbiome analysis. We assessed the colonic microbiota and the expression of specific host response genes in normal colonic mucosal samples from 8 healthy individuals and samples from 20 Egyptian CRC patients. A retrospective convenience sample design was employed. Colonoscopy was performed on these patients at Alexandria University Hospital, Alexandria, Egypt. Microbiota composition was determined by 16S rRNA amplicon sequencing. A panel of 784 genes involved in tumor, microenvironment, and immune response were used to characterize differential expression across patient groups by the Nanostring method. This panel facilitates the estimation of immune cell abundance for 15 tumor-infiltrating immune cell types. Differential abundance and cross-talk between the relative abundance of microbiota and tumor RNA expression were evaluated using negative binomial model fitting and Wald statistics. One third of our CRC patient population was under 50 years old at the time of diagnosis with CRC, and most were female. Healthy controls were even younger than CRC cases, and most were females. There were differences in relative abundances of bacteria between healthy controls and those with CRCs. Analysis showed a low abundance of Mitsuokella multacida, a short-chain fatty acid (SCFA)-producing bacterium, in CRC patients when compared to healthy individuals. In particular, this trend was evident for older CRC patients (≥ 50 years); of note, this bacterium was absent in younger patients (&amp;lt;50 years) (adj. p-value = 0.01). Further, there was a high abundance of Fusobacterium nucleatum in all CRC patients compared to healthy individuals (adj. p-value = 0.04). In cross-talk analysis for healthy controls, elevated abundance of M. multacida was inversely associated with macrophage abundance (global p-value =0.055).For Egyptian patients, the absence of SCFA-producing multacida in younger patients may be a reason for early onset of CRC. These findings suggest that the oncoprotective effect of Mitsuokella multacida should be further investigated. These studies are supported by the US-Egypt STDF grants (NAS 2000007148 and 144/17) and the Impact funds of University of Alabama at Birmingham. Citation Format: Amr Elkholy, Michael Behring, Mohammed Mohsen, Prachi Bajpai, Amira Embaby, Doaa Header, Reham Abo Elwafa, Hesham Saeed, Mona Fouad, Waleed Arafat, Upender Manne. Absence of Mitsuokella multacida is associated with early onset of colorectal cancer [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 6103.