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Gene-expression patterns at transcriptional ans translational levels in the tissues of colorectal cancer are different from that in the correspondent adjacent regions

ABSTRACT: In the interest of gene expression status responsive to CRC, the colorectal tissues from the tumor and adjacency were isolated from the AOM/DSS mouse model, and then the transcriptomes and proteomes in these tissues were quantitatively profiled using next generation sequencing (NGS) and liquid chromatography mass spectrometry (LC-MS). The mutations in the transcriptomes exhibited huge diversity at either site or gene, while a few of mutated peptide were identified in these CRC tissues. Surprisingly, the inconsistent mutations in the gene expression transcriptional products were poorly supported by the genomic data at somatic mutations from the same mouse model. However, quantitative transcriptomic and proteomic data unveiled in the common and clearly differential patterns that enabled a distinction between the tumor and adjacent tissues, implying gene expression status as the sensitive indicators to characterize the CRC-related molecular features. The differentially expressed genes (DEGs) were enriched in the process of environmental information, while the differentially expressed proteins (DEPs) were concentrated in the metabolic pathways. Analysis towards the abundance of expressed products further clarified that most transcripts at lower abundance belonged to the genes within signaling pathways and most transcripts and proteins at higher abundance came from the genes located functioned in metabolism. Collecting transcriptomic and proteomic data in the cancer genome atlas (TCGA) and adopting the similar analysis strategy, the gene expression patterns were compared between human and mouse CRC. The functional themes of the cancer-related genes derived from transcriptomic as well as proteomic evidence in the mouse CRC were quite similar to that in human CRC. The CRC model upon the AOM/DSS mouse is therefore well mimic to human CRC.

ORGANISM(S): Mus musculus

PROVIDER: GSE124029 | GEO | 2019/05/01

REPOSITORIES: GEO

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Project description:Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains M-bM-^@M-^\inflammation-dysplasia-cancerM-bM-^@M-^] sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC. 6-week-old male ICR mice were given a single intraperitoneal injection of AOM (10mg/kg) at Day 1, followed by three cycles of DSS administration (cycle 1: 2%, Day 8~14; cycle 2: 1.5%, Day 29~33; cycle 3: 1.5%, Day 50~54) in the drinking water. Instead, control group of mice were given a single intraperitoneal injection of saline (10mg/kg) at Day 1 and distilled water drinking from the beginning to the end without DSS. Colorectal tissues were collected at days 14, 28, 42, 56 and 140 (at the end of the 2nd, 4th, 6th, 8th and 20th week) from the AOM/DSS group and at day 14 from the control group. Pathological changes of each sample were identified under microscope. Samples collected at the end of the 2nd week were inflamed mucosae, the 4th week were low grade dysplasias, the 6th week were high grade dysplasias, the 8th week were high grade dysplasias with active inflammation, the 20th week were carcinomas, and the control sample were normal mucosae. Total RNA were extracted and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.

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Gene-expression patterns at transcriptional ans translational levels in the tissues of colorectal cancer are different from that in the correspondent adjacent regions

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