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A Seven-NF-?B-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma.

ABSTRACT: Purpose: Ulcerative colitis (UC) patients have an increased risk of colorectal cancer (CRC), and compared with sporadic CRC, ulcerative colitis-associated colorectal cancer (CAC) is more aggressive with a worse prognosis. This study aimed to identify a gene signature to predict the risk of CAC for patients with UC in remission.

Patients and methods: Series of quiescent UC-related transcriptome data obtained from the Gene Expression Omnibus (GEO) data set were divided into a training set and a validation set. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and \Weighted Correlation Network Analysis (WGCNA) combined with protein-protein interaction (PPI) analysis were used to identify the pathways and gene signatures related to tumorigenesis among quiescent UC patients. A generalized linear model (GLM) of Poisson regression based on the training set was applied to estimate the diagnostic power of the gene signature in our validation set.

Results: The tumor necrosis factor (TNF) signaling via NF-?B pathway was significantly augmented with the highest normalized enrichment score (NES). The genes in the brown module from WGCNA have shown a significant correlation with CAC (Pearson coefficient = 0.83, p = 6e-06). A subset of NF-?B related genes (FOS, CCL4, CXCL1, MYC, CEBPB, ATF3, and JUNB) were identified with a relatively higher expression level in CAC samples. The diagnostic value of this 7-gene biomarker was estimated by the receiver operating characteristic (ROC) curve with an area under the ROC curve (AUC) at 0.82 (p<0.0001, 95% CI: 0.7098-0.9400) in the validation cohort.

Conclusion: In summary, the increased expression of this seven-NF-?B-related gene signature may act as a powerful index for tumorigenesis prediction among patients with UC in remission.

SUBMITTER: Ge CY

PROVIDER: S-EPMC7719442 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Seven-NF-κB-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma.

Ge Chao-Yi CY Wei Li-Yuan LY Tian Yu Y Wang Hua-Hong HH

Pharmacogenomics and personalized medicine 20201202

<h4>Purpose</h4>Ulcerative colitis (UC) patients have an increased risk of colorectal cancer (CRC), and compared with sporadic CRC, ulcerative colitis-associated colorectal cancer (CAC) is more aggressive with a worse prognosis. This study aimed to identify a gene signature to predict the risk of CAC for patients with UC in remission.<h4>Patients and methods</h4>Series of quiescent UC-related transcriptome data obtained from the Gene Expression Omnibus (GEO) data set were divided into a training ...[more]

PMID: 33299340

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Project description:BackgroundPatients 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.MethodologyFirstly, 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 findingsIn 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.ConclusionsThe 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.

Dataset Information

A Seven-NF-?B-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma.

Publications

A Seven-NF-κB-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma.

Similar Datasets

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