Dataset Information

Functional comparison between genes dysregulated in ulcerative colitis and colorectal carcinoma.

ABSTRACT:

Background

Patients with ulcerative colitis (UC) are predisposed to colitis-associated colorectal cancer (CAC). However, the transcriptional mechanism of the transformation from UC to CAC is not fully understood.

Methodology

Firstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression. Secondly, based on multiple datasets for UC and CRC, we extracted differentially expressed (DE) genes in UC and CRC versus normal controls, respectively. Thirdly, we compared the dysregulation directions (upregulation or downregulation) between DE genes of UC and CRC in CRC-related functions overrepresented with the DE genes of CRC, and proposed a regulatory model to explain the CRC-like dysregulation of genes in UC. A case study for "positive regulation of immune system process" was done to reveal the functional implication of DE genes with reversal dysregulations in these two diseases.

Principal findings

In all the 44 detected CRC-related functions except for "viral transcription", the dysregulation directions of DE genes in UC were significantly similar with their counterparts in CRC, and such CRC-like dysregulation in UC could be regulated by transcription factors affected by pro-inflammatory stimuli for colitis. A small portion of genes in each CRC-related function were dysregulated in opposite directions in the two diseases. The case study showed that genes related to humoral immunity specifically expressed in B cells tended to be upregulated in UC but downregulated in CRC.

Conclusions

The CRC-like dysregulation of genes in CRC-related functions in UC patients provides hints for understanding the transcriptional basis for UC to CRC transition. A small portion of genes with distinct dysregulation directions in each of the CRC-related functions in the two diseases implicate that their reversal dysregulations might be critical for UC to CRC transition. The cases study indicates that the humoral immune response might be inhibited during the transformation from UC to CRC.

SUBMITTER: Zhao W

PROVIDER: S-EPMC3750042 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional comparison between genes dysregulated in ulcerative colitis and colorectal carcinoma.

Zhao Wenyuan W Qi Lishuang L Qin Yao Y Wang Hongwei H Chen Beibei B Wang Ruiping R Gu Yunyan Y Liu Chunyang C Wang Chenguang C Guo Zheng Z

PloS one 20130822 8

<h4>Background</h4>Patients with ulcerative colitis (UC) are predisposed to colitis-associated colorectal cancer (CAC). However, the transcriptional mechanism of the transformation from UC to CAC is not fully understood.<h4>Methodology</h4>Firstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression. Secondly, based on multiple datasets for UC and CRC, we extracted differentially expressed (DE) genes in UC and CRC versus normal controls, respectively. Thirdly, we co ...[more]

PMID: 23991021

Similar Datasets

Project description:BACKGROUND:The TGF?-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression. METHODS:In this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGF?-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19.0). We utilize paired carcinoma and normal tissue from 217 CRC cases. We evaluate the associations between differentially expressed genes and miRNAs and sex, age, disease stage, and survival months. RESULTS:Thirteen genes were significantly downregulated and 14 were significantly upregulated after considering fold change (FC) of?>?1.50 or?<?0.67 and multiple comparison adjustment. Bone morphogenetic protein genes BMP5, BMP6, and BMP2 and growth differentiation factor GDF7 were downregulated. BMP4, BMP7, INHBA (Inhibin beta A), TGFBR1, TGFB2, TGIF1, TGIF2, and TFDP1 were upregulated. In general, genes with the greatest dysregulation, such as BMP5 (FC 0.17, BMP6 (FC 0.25), BMP2 (FC 0.32), CDKN2B (FC 0.32), MYC (FC 3.70), BMP7 (FC 4.17), and INHBA (FC 9.34) showed dysregulation in the majority of the population (84.3, 77.4, 81.1, 80.2, 82.0, 51.2, and 75.1% respectively). Four genes, TGFBR2, ID4, ID1, and PITX2, were un-associated or slightly upregulated in microsatellite-stable (MSS) tumors while downregulated in microsatellite-unstable (MSI) tumors. Eight dysregulated genes were associated with miRNA differential expression. E2F5 and THBS1 were associated with one or two miRNAs; RBL1, TGFBR1, TGIF2, and INHBA were associated with seven or more miRNAs with multiple seed-region matches. Evaluation of the joint effects of mRNA:miRNA identified interactions that were stronger in more advanced disease stages and varied by survival months. CONCLUSION:These data support an interaction between miRNAs and genes in the TGF?-signaling pathway in association with CRC risk. These interactions are associated with unique clinical characteristics that may provide targets for further investigations.

Dataset Information

Functional comparison between genes dysregulated in ulcerative colitis and colorectal carcinoma.

Background

Methodology

Principal findings

Conclusions

Publications

Functional comparison between genes dysregulated in ulcerative colitis and colorectal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure