scholarly journals Clinic-Genomic Association Mining for Colorectal Cancer Using Publicly Available Datasets

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fang Liu ◽  
Yaning Feng ◽  
Zhenye Li ◽  
Chao Pan ◽  
Yuncong Su ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Big Data ◽  
Genomic Data ◽  
Gene Expression Omnibus ◽  
Literature Mining ◽  
Association Mining ◽  
Malignant Tumours ◽  
Genetic Syndromes ◽  
Genetic Association Database

In recent years, a growing number of researchers began to focus on how to establish associations between clinical and genomic data. However, up to now, there is lack of research mining clinic-genomic associations by comprehensively analysing available gene expression data for a single disease. Colorectal cancer is one of the malignant tumours. A number of genetic syndromes have been proven to be associated with colorectal cancer. This paper presents our research on mining clinic-genomic associations for colorectal cancer under biomedical big data environment. The proposed method is engineered with multiple technologies, including extracting clinical concepts using the unified medical language system (UMLS), extracting genes through the literature mining, and mining clinic-genomic associations through statistical analysis. We applied this method to datasets extracted from both gene expression omnibus (GEO) and genetic association database (GAD). A total of 23517 clinic-genomic associations between 139 clinical concepts and 7914 genes were obtained, of which 3474 associations between 31 clinical concepts and 1689 genes were identified as highly reliable ones. Evaluation and interpretation were performed using UMLS, KEGG, and Gephi, and potential new discoveries were explored. The proposed method is effective in mining valuable knowledge from available biomedical big data and achieves a good performance in bridging clinical data with genomic data for colorectal cancer.

Genomic Data Management in Big Data Environments: The Colorectal Cancer Case

2018 ◽  
pp. 319-329 ◽  
Author(s):  
Ana León Palacio ◽  
Alicia García Giménez ◽  
Juan Carlos Casamayor Ródenas ◽  
José Fabián Reyes Román
Keyword(s):  
Colorectal Cancer ◽  
Big Data ◽  
Data Management ◽  
Genomic Data ◽  
Cancer Case ◽  
Colorectal Cancer Case

scholarly journals Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Qiaowei Fan ◽  
Lin Guo ◽  
Jingming Guan ◽  
Jing Chen ◽  
Yujing Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
R Package ◽  
Gastrointestinal Diseases ◽  
Gene Expression Omnibus ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Network

Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. Conclusion. The study elucidated the “multiingredient, multitarget, and multipathway” mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.

scholarly journals Identification of Hub Genes Associated With Sensitivity of 5-Fluorouracil Based Chemotherapy for Colorectal Cancer by Integrated Bioinformatics Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ya Wang ◽  
Qunhui Wei ◽  
Yuqiao Chen ◽  
Shichao Long ◽  
Yuanbing Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colorectal Adenocarcinoma ◽  
Malignant Tumors ◽  
Gene Expression Omnibus ◽  
Chemotherapy Response ◽  
Intrinsic Resistance ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Novel Biomarkers

Colorectal cancer (CRC) is one of the most common malignant tumors. 5-fluorouracil (5-FU) has been used for the standard first-line treatment for CRC patients for several decades. Although 5-FU based chemotherapy has increased overall survival (OS) of CRC patients, the resistance of CRC to 5-FU based chemotherapy is the principal cause for treatment failure. Thus, identifying novel biomarkers to predict response to 5-FU based chemotherapy is urgently needed. In the present study, the gene expression profile of GSE3964 from the Gene Expression Omnibus database was used to explore the potential genes related to intrinsic resistance to 5-FU. A gene module containing 81 genes was found to have the highest correlation with chemotherapy response using Weighted Gene Co-expression Network Analysis (WGCNA). Then a protein-protein interaction (PPI) network was constructed and ten hub genes (TGFBI, NID, LEPREL2, COL11A1, CYR61, PCOLCE, IGFBP7, COL4A2, CSPG2, and VTN) were identified using the CytoHubba plugin of Cytoscape. Seven of these hub genes showed significant differences in expression between chemotherapy-sensitive and chemotherapy-resistant samples. The prognostic value of these seven genes was evaluated using TCGA COAD (Colorectal Adenocarcinoma) data. The results showed that TGFBI was highly expressed in chemotherapy-sensitive patients, and patients with high TGFBI expression have better survival.

scholarly journals Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Danial Mehranfard ◽  
Gabriela Perez ◽  
Andres Rodriguez ◽  
Julia M. Ladna ◽  
Christopher T. Neagra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Renin Angiotensin System ◽  
Gene Expression Omnibus ◽  
Data Repository ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Quantitative Expression ◽  
Genes Encoding ◽  
Thimet Oligopeptidase

Hypothesis/Introduction. Recent studies suggest involvement of the renin-angiotensin system (RAS) in cancers, including colorectal cancer (CRC). This study focuses on the association of genes encoding 17 proteins related to the RAS within a Japanese male CRC population. Materials and Methods. Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. Results. Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens. Conclusions. Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.

scholarly journals Identification of Mirna Signature and Key Genes in Colorectal Cancer Lymph Node Metastasis

2021 ◽  
Author(s):  
Xi Wang ◽  
Guangyu Gao ◽  
Zhengrong Chen ◽  
Zhihao Chen ◽  
Mingxiao Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cancer Statistics ◽  
Node Metastasis ◽  
Novel Mirna

Abstract Background: miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis and therapy of colorectal cancer (CRC), whose metastasis to lymph node is closely related to the poor prognosis. The current study aimed to identify the novel gene signatures in the lymph node metastasis of CRC.Methods: GSE56350, GSE70574 and GSE95109 were downloaded from the Gene Expression Omnibus (GEO) database and 569 colorectal cancer statistics were also downloaded from the The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated by using R software. Besides, gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using FunRich. Furthermore, the mRNA-miRNA network was constructed using Cytoscape software. Gene expression level was verified by GEO datasets and forty paired lymph node non-metastasis CRC tissues and lymph node metastatic CRC tissues obtained from patients with CRC using quantitative real-time PCR (qPCR) .Results: In total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering. Moreover, 2 key miRNAs and one gene were identified including hsa-miR-99a, has-miR-100 and heparan sulfate-glucosamine 3-sulfotransferase 2 (HS3ST2). The GEO datasets analysis and qPCR results showed the expression of key miRNA and genes were consistent with that in the bioinformatic analysis. A novel miRNA-mRNA network, hsa-miR-99a-HS3ST2-has-miR-100 was found in lymph node metastasis of CRC after expression analysis, prognostic prediction and experiments confirmation.Conclusions: In summary, the potential miRNAs and genes were found and a novel miRNA-mRNA network was established in CRC lymph node metastasis by systematic bioinformatic analysis and experiments validation, which may be used as potential biomarkers in the development of lymph node metastatic CRC.

scholarly journals Identification of Genes in Patients for Predicting Ulcerative Colitis-Associated Colorectal Cancer

2020 ◽  
Author(s):  
hongyun wei ◽  
qian zhang ◽  
xiaosa chi ◽  
xiaohui yang ◽  
zibin tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Limma Package ◽  
Public Datasets

Abstract BackgroundUlcerative colitis (UC) has been considered as a risk factor for colorectal cancer (CRC). However, effective biomarkers for predicting UC-associated CRC are lacking. Therefore, it is necessary to screen biomarkers associated with UC-related CRC, which could be used to evaluate UC-associated CRC early, and provide possible mechanisms involved in UC-associated CRC. Efficient bioinformatics analysis could help us to explore potential biomarkers.MethodsTwo public datasets, including 44 UC without CRC samples and 17 UC-associated CRC samples were chosen from Gene Expression Omnibus (GEO) database. Sva package was used to remove batch effects, and then we screened out differentially expressed genes (DEGs) with limma package. STRING and Cytoscape were used to achieve protein-protein interaction (PPI) network analysis. The survival curves between high and low gene expression were performed by log rank test based on the cancer genome atlas (TCGA) program. The expression of three identified hub genes was validated based on Oncomine. To validate the expression of three hub genes, we compared the expression of three hub genes between normal and colorectal cancer based on Oncomine.Results405 DEGs were identified, including 256 down-regulated genes and 149 up-regulated genes in UC-associated CRC tissues. 16 hub genes were identified. And among them, RPL6, RPL7, and RPL35 were related to poor prognosis of patients in survival analysis. Higher expression of RPL6, RPL7, and RPL35 was validated in CRC tissues based on Oncomine.ConclusionsOur study showed that overexpressed RPL6, RPL7, and RPL 35 may be potential tumor oncogenes and could act as a prognostic factor in clinical diagnosis and treatment.

Functional and prognostic influence of receptor polymorphisms in the vascular endothelial growth factor system in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15032-e15032
Author(s):  
T. Hansen ◽  
K. G. Spindler ◽  
D. A. Olsen ◽  
R. F. Andersen ◽  
J. Lindebjerg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Concentration ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Malignant Tumours ◽  
Free Survival ◽  
Endothelial Growth Factor

e15032 Background: The vascular endothelial growth factor (VEGF) system plays a key role in the angiogenic process ensuring a sufficient blood supply to the growth of malignant tumours. The clinical importance of single nucleotide polymorphisms (SNP's) in the VEGF receptors is still unknown. The aim of this study was to investigate the functional and prognostic influence of the V297I C/T and the -604 T/C SNP's in the VEGFR-2 gene, in tumour and normal tissue from colorectal cancer patients. Methods: Blood samples and tissue were collected from 110 patients, surgically resected for colorectal cancer. Genomic DNA was isolated from whole blood, and SNP's were analysed by PCR. Gene expression analysis was performed by RT-PCR and protein analysis was performed by ELISA. Progression free survival according to genotypes was compared using the Kaplan-Meier method and the logrank test. Results: Median gene expression according to the CC genotype of the -604 T/C SNP, were significantly higher than the median gene expression of the TT genotype (p = 0.045) and the TC genotype (p = 0.033) in CRC tissue. Regarding the V297I C/T SNP, median protein concentration according to the CT genotype was significantly higher than the median protein concentration of the CC genotype, p = 0.005. The CC genotype held prognostic information compared to CT and TT genotypes for both SNP's, p<0.05. Conclusions: The V297I C/T SNP seems to have a functional influence on the VEGFR-2 protein level, and the -604 T/C SNP on the gene expression level in CRC patients. The results furthermore indicate a prognostic influence of both SNP's on progression-free survival. No significant financial relationships to disclose.

scholarly journals Identification of CXCL8 as an Immune Microenvironment Regulator of Colorectal Cancer: A Bioinformatics Study Based on Cancer Genome Atlas and Gene Expression Omnibus Datasets

2020 ◽  
Author(s):  
Ying Shao ◽  
Shuhua Gao ◽  
Minrong Cheng ◽  
Jinxiu Zheng ◽  
Ting Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
M2 Macrophages ◽  
Immune Microenvironment ◽  
Hub Gene ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract BackgroundAt present, a lack of knowledge of the molecular mechanisms underlying the genesis and progression of colorectal cancer (CRC) exists. This is one of the reasons for poor prognosis of this increasingly occurring disease. The purpose of our research is to identify molecular candidates for therapeutic intervention that would help stop the malignant progression of CRC.MethodsIn this study, we performed bioinformatic analysis of the combined microarray data GSE40967 and GSE8671 in Gene Expression Omnibus (GEO) and the CRC RNA-seq dataset in The Cancer Genome Atlas (TCGA). This analysis consisted of 1067 CRC samples and 92 normal mucosae in total. We identified the common differentially expressed genes (DEGs) using R and Venn software. Protein–protein interaction (PPI) network information was obtained using the Search Tool for the Retrieval of Interacting Genes (STRING) Database. The Cytoscape plug-ins MCODE and cytoHubba were used to screen hub modules. CXCL8, which was the selected hub gene, was subjected to functional analysis and Gene Set Enrichment Analysis (GSEA). The algorithm “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” was employed to estimate the relative abundance of tumor infiltrating lymphocyte cells (TILs) with CXCL8 expression. Finally, correlation analysis was carried out to explore the underlying mechanisms.ResultsWe identified 135 common DEGs, which consisted of 38 upregulated genes and 97 downregulated genes. The upregulated DEGs were strikingly enriched in regulation of neutrophil chemotaxis and cytokine-cytokine receptor interaction. The downregulated DEGs were enriched in bicarbonate transport. We identified the candidate molecule CXCL8 as a product of the hub gene. Functional enrichment analysis and GSEA indicated that CXCL8 may be closely related to a regulator of the CRC immune microenvironment. Finally, TILs analysis and correlation analysis showed that CXCL8 may inhibit CD8+ T cell immune infiltration through the HIF-1α/PD-Ls axis. In addition, CXCL8 could induce the polarization of M2 macrophages through the PI3K/AKT3 pathway.ConclusionsWe determined that hub gene CXCL8 may promote immune escape of CRC by inhibiting CD8+ T cell immune infiltration or promoting polarization of M2 macrophages. CXCL8 is a potential therapeutic target for the treatment of CRC patients.

scholarly journals Construction of a Pseudogene‐associated ceRNA Network and Identification of Prognostic Pseudogene Biomarkers for Colorectal Cancer

2021 ◽  
Author(s):  
Zhuoqi Li ◽  
Jing Zhou ◽  
Liankun Gu ◽  
Baozhen Zhang
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cox Regression ◽  
Expression Profiles ◽  
Colon Adenocarcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Cerna Network ◽  
Kaplan Meier

Abstract Colorectal cancer (CRC) is one of the most common and deadly malignant carcinomas. Many long noncoding RNAs (lncRNA) have been reported to play an important role in the tumorigenesis of CRC by interacting with miRNAs and influencing the expression of some mRNAs through a competing endogenous RNA (ceRNA) network. Pseudogenes are one kind of lncRNA and can act as RNA sponges for miRNAs and regulate gene expression via ceRNA networks, but there are few studies about pseudogenes in CRC. In this study, total of 31 differentially expressed (DE) pseudogenes, 17 DE miRNAs and 152 DE mRNAs were identified by analyzing the expression profiles of colon adenocarcinoma (COAD) obtained from The Cancer Genome Atlas (TCGA). And a ceRNA network was constructed based on these RNAs. Kaplan–Meier analysis showed that 7 pseudogenes, 4 miRNAs and 30 mRNAs were significantly associated with overall survival. Then multivariate Cox regression analysis on the ceRNA-related DE pseudogenes was performed and a 5-pseudogene signature with the greatest prognostic value for CRC was identified. What’s more, the results were validated by the Gene Expression Omnibus (GEO) database, and quantitative real‐time PCR (qRT‐PCR) in 113 pairs of CRC tissues. In conclusion, this study provides a pseudogene-associated ceRNA network and 7 prognostic pseudogene biomarkers, and a 5-pseudogene prognostic risk signature that may be useful to predict the survival of CRC patients.

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