Multi-omics reveals microbiome, host gene expression, and immune landscape in gastric carcinogenesis

Chan Hyuk Park; Changjin Hong; A-Reum Lee; Jaeyun Sung; Tae Hyun Hwang

doi:10.1016/j.isci.2022.103956

Multi-omics reveals microbiome, host gene expression, and immune landscape in gastric carcinogenesis

iScience. 2022 Feb 19;25(3):103956. doi: 10.1016/j.isci.2022.103956. eCollection 2022 Mar 18.

Authors

Chan Hyuk Park¹, Changjin Hong², A-Reum Lee¹, Jaeyun Sung^{3

4}, Tae Hyun Hwang^{2

5}

Affiliations

¹ Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggido 11923, Republic of Korea.
² Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL 32224, USA.
³ Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.
⁴ Division of Surgery Research, Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
⁵ Department of Immunology, Mayo Clinic, Jacksonville, FL 32224, USA.

Abstract

To date, there has been no multi-omic analysis characterizing the intricate relationships between the intragastric microbiome and gastric mucosal gene expression in gastric carcinogenesis. Using multi-omic approaches, we provide a comprehensive view of the connections between the microbiome and host gene expression in distinct stages of gastric carcinogenesis (i.e., healthy, gastritis, cancer). Our integrative analysis uncovers various associations specific to disease states. For example, uniquely in gastritis, Helicobacteraceae is highly correlated with the expression of FAM3D, which has been previously implicated in gastrointestinal inflammation. In addition, in gastric cancer but not in adjacent gastritis, Lachnospiraceae is highly correlated with the expression of UBD, which regulates mitosis and cell cycle time. Furthermore, lower abundances of B cell signatures in gastric cancer compared to gastritis may suggest a previously unidentified immune evasion process in gastric carcinogenesis. Our study provides the most comprehensive description of microbial, host transcriptomic, and immune cell factors of the gastric carcinogenesis pathway.

Keywords: Cellular physiology; Microbiome; Omics.