Study Of Gene Expression In The Inflammation Subtype Of Human CRC And The Inflammatory-to-cancer Model

Colorectal cancer was considered one of the most common malignant tumor, which could be life threatening. According to the gene preferentially expressed, we named five subtypes, including inflammatory subtype. The transition process of inflammatory-to-cancer was complex, and many signaling pathways and molecules were involved. In the current study, we used bioinformatics methods to investigated the expression of the inflammatory factors related in the inflammatory subtype. We also established the colitis-associated colon cancer mouse model, obtained the whole genome expression profiles. Then we investigated the gene expression of inflammatory factors related, and compared with the changes with that in inflammatory subtype of colon cancer.(Part 1) The molecular typing of colorectal cancer is a clinical concern and research focus. And the transition of inflammatory-to-cancer fascinated more and more researchers. Many studies suggested the process of inflammatory-to-cancer existed, but not every cancer was derived from inflammatory. We focused on inflammation subtype of CRC. In this part, we downloaded the genomic data of human CRC and normal control from TCGA database online. We then divided the cases into five subtypes, including the inflammation subtype, and investigated the gene expression changes of ILIA, IL1B, IL6, IL23A, NFKB2, TGFB1, TGFB3, PTGS2 in the inflammation subtype. The results showed that 98 cases of CRC were divided into inflammation subtype, and we found high expression of the eight genes mentioned above.(Part 2) Genomic data downloaded from TCGA database were mainly collected from North America and other countries, the results differs from countries and areas. In this part,67 patients were studied.10 of them were clustered as the inflammation subtype. The changes of ILIA, IL1B, IL6, IL23A, NFKB2, TGFB1, TGFB3, PTGS2 gene expression were investigated. High expression of these genes were found.(Part 3)The animal model played an irreplaceable role in the pathological studies. Among animal models of colitis associated CRC, AOM/DSS model was commonly used since the administration of AOM and DSS caused rapid growth of multiple colon tumors, shorting the latency time. In this part, we established the AOM/DSS mouse model, and obtained whole genome expression profile. The results showed that the mice experienced the changes from normal to colorectal cancer. After three cycles treatment of DSS, all mice had colorectal cancer. By analysising the gene expression of mice treating with different cycles treatment of DSS, we found that as the time passed and the superposition of DSS cycles, Il1a, Il1b,Il6,Il23a, Nfkb2, Tgfb1, Ptgs2 showed high expression, except for Tgfb3, which showed a low expression. And the high expression trended to be more and more significant. The changes of expression were same as that in human inflammation subtype of CRC in Part 1 and Part 2 above.Combining the results of Part 1, Part 2 and Part 3, we believed that CRC is a kind of disease with a high heterogeneity, we could get a molecular classification by gene expression. The rate of inflammatory subtype was similar in both TCGA database and Chinese patients. The inflammatory subtype showed an increased expression of IL1A、 IL1B、IL6、IL23A、NFKB2、TGFB1、TGFB3、PTGS2. The changes of gene expression we investigated were similar in human and mice, which indicated that the AOM/DSS model was also applicable for the study of human inflammation subtype of CRC.But whether the AOM/DSS model can be applied to other types of CRC, we needed further research.