Abstract
ObjectiveTo screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.MethodsThe molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.ResultsThe general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.ConclusionThe pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.
Highlights
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with the third highest morbidity and mortality worldwide [1]
The results showed that the expression of GATA4 and LHPP in the model mice was down-regulated compared with the control mice
The availability of excellent animal models and the similarity of mutation spectra between hereditary and sporadic diseases contribute to our understanding of disease development and progression [22]
Summary
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with the third highest morbidity and mortality worldwide [1]. A number of studies have confirmed that genetics, inflammatory disease, lipid metabolic disorders, and sugar metabolic disorders are risk factors for the onset of colorectal adenomas [6]. The adenoma model of inflammatory cancer transformation is one of the commonly used models to study the carcinogenesis of CRC [7, 8]. The establishment of human disease simulated animal model has important scientific value, and the use of animal model for experimental research is very important [10], which is convenient and effective in understanding the mechanisms of disease occurrence and development and research on prevention and control measures, and can avoid the risk brought by human experiments [11]
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