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

Zhao W, Qi L, Qin Y, Wang H, Chen B, Wang R, Gu Y, Liu C, Wang C, Guo Z - PLoS ONE (2013)

Bottom Line: Firstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression.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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

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.

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Related in: MedlinePlus

The CRC-related functions in the directed acyclic graph of Biological Process.A. All the CRC-related functions. B. A case for both the ancestor and offspring terms retained simultaneously. C. A case for just one term retained in a biological process branch.
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pone-0071989-g001: The CRC-related functions in the directed acyclic graph of Biological Process.A. All the CRC-related functions. B. A case for both the ancestor and offspring terms retained simultaneously. C. A case for just one term retained in a biological process branch.

Mentions: Then, using the GO-function algorithm, with FDR control of 1%, we selected 44 CRC-related terms located in different branches of the directed acyclic graph of biological process, as shown in Figure 1A. Some of these CRC-related terms had ancestor-offspring relationships. For example, as shown in Figure 1B, the “mitosis” and its three offspring terms “mitotic prometaphase”, “mitotic metaphase/anaphase transition” and “regulation of mitosis” were retained simultaneously. It is known that the “mitosis” is related to cancer [33], whereas the three offspring terms are important steps in the mitosis [34]. In general, most of the 44 terms such as “apoptosis” and “cell proliferation” were well known cancer-associated functions, and many other terms could also be explained. For example, as shown in Figure 1C, the significant term “cellular component biogenesis at cellular level” includes “membrane biogenesis” and “nucleologenesis” as offspring terms which are necessary for mitosis whose dysregulation is related to the abnormal proliferation of cancer cells [35]. For another example, the significant term “macromolecule modification” includes “DNA modification”, “RNA modification”, “protein modification process” and “macromolecule methylation” as offspring terms, with the type of modification being, besides others, methylation such as DNA methylation or demethylation associated with carcinogenesis [36], [37]. Similarly, for the significant term “interspecies interaction between organisms”, accumulated evidences indicate that interaction between intestinal bacteria and host is significantly related with the occurrence and development of the CRC [38], [39].


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

Zhao W, Qi L, Qin Y, Wang H, Chen B, Wang R, Gu Y, Liu C, Wang C, Guo Z - PLoS ONE (2013)

The CRC-related functions in the directed acyclic graph of Biological Process.A. All the CRC-related functions. B. A case for both the ancestor and offspring terms retained simultaneously. C. A case for just one term retained in a biological process branch.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750042&req=5

pone-0071989-g001: The CRC-related functions in the directed acyclic graph of Biological Process.A. All the CRC-related functions. B. A case for both the ancestor and offspring terms retained simultaneously. C. A case for just one term retained in a biological process branch.
Mentions: Then, using the GO-function algorithm, with FDR control of 1%, we selected 44 CRC-related terms located in different branches of the directed acyclic graph of biological process, as shown in Figure 1A. Some of these CRC-related terms had ancestor-offspring relationships. For example, as shown in Figure 1B, the “mitosis” and its three offspring terms “mitotic prometaphase”, “mitotic metaphase/anaphase transition” and “regulation of mitosis” were retained simultaneously. It is known that the “mitosis” is related to cancer [33], whereas the three offspring terms are important steps in the mitosis [34]. In general, most of the 44 terms such as “apoptosis” and “cell proliferation” were well known cancer-associated functions, and many other terms could also be explained. For example, as shown in Figure 1C, the significant term “cellular component biogenesis at cellular level” includes “membrane biogenesis” and “nucleologenesis” as offspring terms which are necessary for mitosis whose dysregulation is related to the abnormal proliferation of cancer cells [35]. For another example, the significant term “macromolecule modification” includes “DNA modification”, “RNA modification”, “protein modification process” and “macromolecule methylation” as offspring terms, with the type of modification being, besides others, methylation such as DNA methylation or demethylation associated with carcinogenesis [36], [37]. Similarly, for the significant term “interspecies interaction between organisms”, accumulated evidences indicate that interaction between intestinal bacteria and host is significantly related with the occurrence and development of the CRC [38], [39].

Bottom Line: Firstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression.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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

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.

Show MeSH
Related in: MedlinePlus