Identification of genes in ulcerative colitis associated colorectal cancer based on centrality analysis of co-expression network

Zhu, Jinming; Li, C; Ji, Wilson

doi:10.4149/neo_2015_090

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…For CRA, a study by Mclean et al showed that the inflammatory cytokine genes CXCL1, CXCL2, CXCL3, CCL20, IL8 (CXCL8), CCL23, CCL19, CCL21, and CCL5are BioMed Research International 4) and CEACAM7 (carcinoembryonic antigen-related cell adhesion molecule 7) have been found to be associated with an unfavourable prognosis in CRC [41]. SLC4A4 was also found to be a differentially expressed gene common to UC and CRC [42]. The downregulation of CEACAM7 expression in hyperplastic polyps and early adenomas represents some of the earliest observable molecular events leading to CRC [43].…”

Section: Discussionmentioning

confidence: 99%

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

Zhou

Xie

Cui

et al. 2020

BioMed Research International

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Background. This study is aimed at identifying unknown clinically relevant genes involved in colorectal cancer using bioinformatics analysis. Methods. Original microarray datasets GSE107499 (ulcerative colitis), GSE8671 (colorectal adenoma), and GSE32323 (colorectal cancer) were downloaded from the Gene Expression Omnibus. Common differentially expressed genes were filtered from the three datasets above. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, followed by construction of a protein-protein interaction network to identify hub genes. Kaplan-Meier survival analysis and TIMER database analysis were used to screen the genes related to the prognosis and tumour-infiltrating immune cells of colorectal cancer. Receiver operating characteristic curves were used to assess whether the genes could be used as markers for the diagnosis of ulcerative colitis, colorectal adenoma, and colorectal cancer. Results. A total of 237 differentially expressed genes common to the three datasets were identified, of which 60 were upregulated, 125 were downregulated, and 52 genes that were inconsistently up- and downregulated. Common differentially expressed genes were mainly enriched in the cellular component of extracellular exosome and integral component of membrane categories. Eight hub genes, i.e., CXCL3, CXCL8, CEACAM7, CNTN3, SLC1A1, SLC16A9, SLC4A4, and TIMP1, were related to the prognosis and tumour-infiltrating immune cells of colorectal cancer, and these genes have diagnostic value for ulcerative colitis, colorectal adenoma, and colorectal cancer. Conclusion. Three novel genes, CNTN3, SLC1A1, and SLC16A9 were shown to have diagnostic value with respect to the occurrence of colorectal cancer and should be verified in future studies.

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Section: Discussionmentioning

confidence: 99%

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

Zhou

Xie

Cui

et al. 2020

BioMed Research International

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“…Fortunately, some researchers hold that hub analysis of the coexpression network could overcome this limitation to some degree ( 42 , 43 ). Closeness is one of the most important metrics for finding hubs in a network ( 27 , 44 ). Closeness is the length of the shortest path from one node to another.…”

Section: Discussionmentioning

confidence: 99%

“…Closeness centrality of a certain node is the combined shortest distance from all other nodes. Closeness centrality represents the potent influence of a node on the network ( 27 ). The closeness scores of nodes in the coexpression network were calculated using the CytoHubba plug-in ( 28 ) in Cytoscape.…”

Section: Methodsmentioning

confidence: 99%

Diosgenin protects against alveolar bone loss in ovariectomized rats via regulating long non‑coding RNAs

et al. 2018

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The present study assessed the changes in long non-coding (lnc)RNA and mRNA expression profiles when diosgenin (DIO) exerted a potential osteoprotective effect on the alveolar bone of ovariectomized (OVX) rats. Female Wistar rats underwent a sham operation (SHAM group) or ovariectomy. OVX rats were treated using vehicle (OVX group), DIO (DIO group) or estradiol valerate (EV group) for 12 weeks. After treatment, the biomarkers of bone turnover in plasma and the microstructure of alveolar bone were assessed. lncRNA microarrays were applied to assess lncRNA and mRNA expression profiles in alveolar bone in the OVX and DIO group rats. Subsequently, the differentially expressed mRNAs associated with the comprehensive bone metabolism pathway in Ingenuity Pathway Analysis (IPA) were identified and regarded as key mRNAs. Based on some of the key mRNAs and all the differentially expressed lncRNAs, a coexpression network was established and this network was further analyzed to identify the top 6 lncRNAs with the highest closeness scores (pivotal lncRNAs). Finally, 6 modules showing interactions between pivotal lncRNAs and key mRNAs were constructed. All of the pivotal lncRNAs and key mRNAs were validated with reverse transcription-quantitative polymerase chain reaction. The present findings demonstrated that DIO suppressed the loss of alveolar bone in OVX rats, and the changes to the expression of some lncRNAs or mRNAs occurred in the alveolar bone of the rats in the DIO group. Twenty-four key mRNAs were identified during pathway analysis. Furthermore, 8/24 key mRNAs (Ctnnb1, Smad4, Tcf2, Sp7, Il1b, Il1r1, Tnf and Tnfrsf1a) were used to establish a coexpression network, which included 1,656 nodes and 5,341 edges. During network analysis, 6 pivotal lncRNAs (XR_008346, MRuc007iji, MRAK157089, MRAK076413, MRAK143591 and AB036696) were obtained, and 6 modules illustrating pivotal lncRNA-key mRNA interactions were identified. These results revealed that the anti-osteoporotic effect of DIO on alveolar bone may be associated with the promotion of a bone formation process through increasing the signaling of the Wnt and BMPs pathways and the inhibition of the bone resorption process through decreasing stimulators of osteoclastogenesis. To conclude, several pivotal lncRNAs may serve important roles in these processes via regulating some key mRNAs in the bone metabolism pathway.

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“…Overall, primary tumors and their paired metastases frequently revealed many genes to be altered in common at both sites; these findings support the existence of a very close genomic relationship between the GEP of primary colorectal tumors and their paired liver metastases, as it has also been suggested to occur at the DNA level [16]. Deregulated expression observed in common in both groups of (paired) tumor samples included increased expression of genes linked to liver metastatic sCRC, tumor development, growth (TACSTD2) [17] and invasiveness (FOXQ1, MMP7 and CLDN1) [18, 19], together with decreased expression of genes related to differentiation (CLCA4, CLCA1 and AQP8) [20, 21], apoptosis (CA1) [22], immunity (ZG16) [23], and protection (FCGBP and CA2) [24] of CRC cells. Thus, the functional networks most strongly affected in primary tumors included those involved in focal adhesion, PI3K-Akt and ErbB signaling and other cancer pathways, FcδR-mediated phagocytosis, endocytosis, bacterial invasion of epithelial cells, plus the TP53 signaling pathway, all of which have been previously shown to be directly involved in the development and progression of sCRC [25–29].…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of liver metastases from colorectal cancer patients

et al. 2016

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Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFβ signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis.

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Identification of genes in ulcerative colitis associated colorectal cancer based on centrality analysis of co-expression network

Cited by 5 publications

References 42 publications

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

Diosgenin protects against alveolar bone loss in ovariectomized rats via regulating long non‑coding RNAs

Genomic characterization of liver metastases from colorectal cancer patients

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