title: Identification of gene expression changes from colitis to CRC in the mouse CAC model.
abstract: A connection between colorectal carcinogenesis and inflammation is well known, but the underlying molecular mechanisms have not been elucidated. Chemically induced colitis-associated cancer (CAC) is an outstanding mouse model for studying the link between inflammation and cancer. Additionally, the CAC model is used for examining novel diagnostic, prognostic, and predictive markers for use in clinical practice. Here, a CAC model was established in less than 100 days using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice. We examined the mRNA expression profiles of three groups: control untreated mice (K), DSS-induced chronic colitis mice (D), and AOM/DSS-induced CAC (AD) mice. We identified 6301 differentially expressed genes (DEGs) among the three groups, including 93 persistently upregulated genes and 139 persistently downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the most persistent DEGs were significantly enriched in metabolic or inflammatory components in the tumor microenvironment. Furthermore, several associated DEGs were identified as potential DEGs by protein-protein interaction (PPI) network analysis. We selected 14 key genes from the DEGs and potential DEGs for further quantitative real-time PCR (qPCR) verification. Six persistently upregulated, 3 persistently downregulated DEGs, and the other 3 genes showed results consistent with the microarray data. We demonstrated the regulation of 12 key genes specifically involved in Wnt signaling, cytokine and cytokine receptor interactions, homeostasis, and tumor-associated metabolism during colitis-associated CRC. Our results suggest that a close relationship between metabolic and inflammatory mediators of the tumor microenvironment is present in CAC.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Department of Respiratory Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yan Mei
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yanqiao
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding
chemical_list: D016264:Dextran Sulfate; D001397:Azoxymethane
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