Analysis of Potential Genes and Pathways Involved in the Pathogenesis of Acne by Bioinformatics

Acne is the eighth most frequent disease worldwide. Inflammatory response runs through all stages of acne. It is complicated and is involved in innate and adaptive immunity. This study aimed to explore the candidate genes and their relative signaling pathways in inflammatory acne using data mining analysis. Microarray data GSE6475 and GSE53795, including 18 acne lesion tissues and 18 matched normal skin tissues, were obtained. Differentially expressed genes (DEGs) were filtered and subjected to functional and pathway enrichment analyses. Protein–protein interaction (PPI) network and module analyses were also performed based on the DEGs. In this work, 154 common DEGs, including 145 upregulated and 9 downregulated, were obtained from two microarray profiles. Gene Ontology and pathway enrichment of DEGs were clustered using significant enrichment analysis. A PPI network containing 110 nodes/DEGs was constructed, and 31 hub genes were obtained. Four modules in the PPI network, which mainly participated in chemokine signaling pathway, cytokine–cytokine receptor interaction, and Fc gamma R-mediated phagocytosis, were extracted. In conclusion, aberrant DEGs and pathways involved in acne pathogenesis were identified using bioinformatic analysis. The DEGs included FPR2, ITGB2, CXCL8, C3AR1, CXCL1, FCER1G, LILRB2, PTPRC, SAA1, CCR2, ICAM1, and FPR1, and the pathways included chemokine signaling pathway, cytokine–cytokine receptor interaction, and Fc gamma R-mediated phagocytosis. This study could serve as a basis for further understanding the pathogenesis and potential therapeutic targets of inflammatory acne.

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Identification of primary genes in glomeruli compartment of immunoglobulin A nephropathy by bioinformatic analysis

PeerJ ◽

10.7717/peerj.7067 ◽

2019 ◽

Vol 7 ◽

pp. e7067

Author(s):

Mohammed Khamis Miraji ◽

Yichun Cheng ◽

Shuwang Ge ◽

Gang Xu

Keyword(s):

Extracellular Matrix ◽

Expression Profiles ◽

Immunoglobulin A ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Ppi Network ◽

Immunoglobulin A Nephropathy ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway

The current study is aimed to explore the specific genes which are responsible for the manifestation of Immunoglobulin A nephropathy (IgAN). Gene expression profiles GSE37460, GSE93798 and GSE104948 were analyzed using biological informatics methods to identify differentially expressed genes (DEGs) in IgAN glomeruli samples which were then compared to normal control samples. Subsequently, the DEGs were overlapped to explore genes with significant expression in at least two profiles. Finally, the enrichment analysis was conducted and the protein-protein interaction (PPI) network was constructed for the overlapping DEGs. A total of 28 genes were up-regulated and 10 genes were down-regulated. The up-regulated genes including CD44 and FN1 were chiefly involved in extracellular matrix receptors interaction pathway. In addition, CX3CR1 and CCL4 were associated with chemokine signaling pathway. ITGB2, PTPRC, FN1, and FCER1G were hub genes with a high degree of interaction in the PPI network. Therefore, this study identified many significant genes associated with extracellular matrix expansion and inflammatory mechanism which may be the novel biomarker and target candidates in IgAN.

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Identification of Genes and Pathways Associated with Acne Using Integrated Bioinformatics Methods

Dermatology ◽

10.1159/000502203 ◽

2019 ◽

Vol 235 (6) ◽

pp. 445-455 ◽

Cited By ~ 6

Author(s):

Xianglan Li ◽

Yuxi Jia ◽

Shiyi Wang ◽

Tianqi Meng ◽

Mingji Zhu

Keyword(s):

Expression Profiles ◽

Killer Cell ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Cytokine Receptor ◽

Gene Set Enrichment Analysis ◽

Receptor Interaction ◽

Ppi Network ◽

Ncbi Gene Expression Omnibus ◽

Chemokine Signaling

Background: Acne is the most common skin inflammatory condition. The pathogenesis of acne is not fully understood. Aims: We performed weighted gene co-expression network analysis (WGCNA) to select acne-associated genes and pathways. Methods: GSE53795 and GSE6475 datasets including data from lesional and nonlesional skin of acne patients were downloaded from the NCBI Gene Expression Omnibus. Differentially expressed genes (DEGs) in lesions were identified following a false discovery rate <0.05 and | log2 fold change | ≥0.5. DEG-associated biological processes and pathways were identified. WGCNA analysis was performed to identify acne-associated modules. DEGs in the acne-associated modules were used for protein-protein interaction (PPI) network construction and Gene Set Enrichment Analysis (GSEA). Acne-associated candidate DEGs and pathways were identified together with items in the Comparative Toxicogenomics Database (CTD). Results: A total of 2,140 and 1,190 DEGs were identified in GSE53795 and GSE6475 datasets, respectively, including 716 overlapping DEGs with similar expression profiles in the two datasets, which were clustered into 10 consensus modules. Two modules (brown and turquoise, 359 genes) were associated with acne phenotype. Of these 359 DEGs, 254 were enrolled in the PPI network. GSEA showed that these DEGs were associated with chemokine signaling pathway, cytokine-cytokine receptor interaction, and natural killer cell-mediated cytotoxicity. After identification in CTD, one pathway Cytokine-cytokine receptor interaction and 24 acne-associated DEGs, including IL1R1, CXCL1, CXCR4, CCR1, CXCL2 and IL1β, were identified as candidates associated with acne. Conclusion: Our results highlight the important roles of the proinflammatory cytokines including IL1β, CXCL1, CXCL2, CXCR4, and CCR1 in acne pathogenesis or therapeutic management.

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Mammary Transcriptome Profile during Peak and Late Lactation Reveals Differentially Expression Genes Related to Inflammation and Immunity in Chinese Holstein

Animals ◽

10.3390/ani10030510 ◽

2020 ◽

Vol 10 (3) ◽

pp. 510

Author(s):

Ziyin Han ◽

Yongliang Fan ◽

Zhangping Yang ◽

Juan J. Loor ◽

Yi Yang

Keyword(s):

Mammary Gland ◽

Signaling Pathway ◽

Receptor Interaction ◽

Gene Expressions ◽

Chinese Holstein ◽

Chemokine Signaling ◽

Transcriptomic Sequencing ◽

Receptor Signaling Pathway ◽

Differential Expressed Genes ◽

Chemokine Signaling Pathway

Somatic cell count (SCC) in milk is widely used in the dairy industry, as an indicator of the health of mammary gland. While the SCC of dairy cattle was higher in late lactation than in peak lactation, its association with gene expressions of mammary gland were largely unknown. In this study, a transcriptomic sequencing approach and bioinformatics analysis were used to investigate the differential expressed genes (DEGs) associated with inflammation and immunity between peak and late periods of lactation in Chinese Holstein. A total of 446 DEGs (padj < 0.05 and fold change >2) were identified, 50 of which belonged to seven pathways and five terms related to inflammation and immunity. Our data suggested that the activation of nuclear transcription factor-κB (NF-κB) pathway and Toll-like receptor signaling pathway caused inflammatory response, and the activation of chemokine signaling pathway and cytokine–cytokine receptor interaction signaling pathway caused a protective immune response to ensure dairy cows health during late lactation. Our findings deepen the understanding of the molecular mechanism and physiological functions of mammary inflammation in Chinese Holstein during late lactation.

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MIR502 Acts As a Tumor Suppressor Gene to Accelerate Apoptosis and Suppress Proliferation by Targeting Hippo Signaling Pathway in Ovarian Cancer

10.21203/rs.3.rs-27546/v1 ◽

2020 ◽

Author(s):

Yan Li ◽

Qi Wang ◽

Ning Ning ◽

Fanglan Tang ◽

Yan Wang

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Suppressor Gene ◽

Hippo Signaling ◽

Ppi Network ◽

Pathway Enrichment ◽

Hippo Signaling Pathway ◽

Upstream Regulator

Abstract Background Ovarian cancer (OC) is the major cause of death among women due to the lack of early screening methods and complex pathological progression. Increasing evidence indicated that microRNAs were considered as gene expression regulators in tumors by interacting with mRNAs. Although researches regarding with OC and microRNAs are extensive, the vital role of MIR502 in OC still remains unclear.Methods We integrated two microRNA expression arrays from GEO to identify differentially expressed genes. Kaplan–Meier method was used to screen miRNAs that had influence on survival outcome. Upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study correlated genes with MIR502. Gene Set Enrichment Analysis (GSEA) was conducted to reveal the functional annotation of GO and KEGG pathway enrichment analysis by using the open access WebGestalt tool. We constructed PPI network by using the STRING to further explore core protein.Results We found that expression level of MIR502 was significantly down regulated in OC, which was related to poor overall survival outcome. NRF1 as the upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. In addition, anti-apoptosis and pro-proliferation genes attending in Hippo signaling pathway, including CCND1, MYC, FGF1 and GLI2 were negatively regulated by MIR502 in the analysis of GO and KEGG pathway enrichment results. PPI network further demonstrated that CCND1 and MYCN were at core position in the development of ovarian cancer.Conclusions MIR502, which was regulated by NRF1, acted as a tumor suppressor gene to accelerate apoptosis and suppress proliferation by targeting Hippo signaling pathway in ovarian cancer.

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The study of the significance and prognosis of the differential expressed miRNAs and their target genes associated with biological in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15088 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15088-e15088

Author(s):

Mingyun Wang ◽

Mi Yang

Keyword(s):

Colorectal Cancer ◽

Target Genes ◽

Biological Significance ◽

Differentially Expressed ◽

Prognostic Indicators ◽

Receptor Interaction ◽

Ppi Network ◽

Prognostic Information ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway

e15088 Background: MicroRNAs (miRNAs) have been related to prognostic indicators (such as stage and survival) in colorectal cancer. This study aimed to identify differentially expressed miRNAs and their target genes associated with biological significance and prognosis in colorectal cancer. Methods: The colorectal cancer, colorectal adenoma, and normal samples were obtained from the gene expression profile of GSE71187. A union of differentially expressed genes (DEGs) in the three groups was identified. The significantly different modules with highly interconnected DEGs were identified using weighted correlation network analysis (WGCNA) and were enriched to the KEGG pathway and GO function. Subsequently, the protein-protein interaction (PPI) network for DEGs in the module and the integrated regulatory network of miRNA-DEGs were constructed. In addition, the relationship of target DEGs and prognostic information was analyzed. Results: Three significantly different modules were identified, such as the brown, turquoise, and grey modules. The turquoise module including LTC4S, KLRK1, UNC5C, etc., which was mainly enriched to cell adhesion, cytokine−cytokine receptor interaction, and chemokine signaling pathway, inhibited the development of colorectal cancer. Subsequently, PPI network was constructed with the 678 DEGs in the three modules. Moreover, the miRNA-DEGs network was constructed with the 17 target DEGs (CXCR1, LTC4S, BTK, IGF1, etc.) and 14 miRNA (hsa-miR-335-5p, etc.). Finally, the overexpressed LTC4S was a good prognostic biomarker for colorectal cancer. Conclusions: The hsa-miR-335-5p might have potential prognosis value by targeting LTC4S and CXCR1 in colorectal cancer.

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Identification of hub genes and pathways in psoriasis through bioinformatics and validation by RT-qPCR

10.21203/rs.3.rs-357690/v1 ◽

2021 ◽

Author(s):

Ling Ai Zou ◽

Qichao Jian

Keyword(s):

Signaling Pathway ◽

Quantitative Polymerase Chain Reaction ◽

Cytokine Receptor ◽

Receptor Interaction ◽

Hacat Cells ◽

Receptor Signaling ◽

Ppi Network ◽

Hub Genes ◽

Network Analyses ◽

Receptor Signaling Pathway

Abstract Background Although several studies have attempted to investigate the aetiology and mechanism of psoriasis, the precise molecular mechanism remains unclear. Our study aimed to identify the hub genes and associated pathways that promote its pathogenesis in psoriasis, which would be helpful for the discovery of diagnostic and therapeutic markers. Methods GSE30999, GSE34248, GSE41662, and GSE50790 datasets were extracted from the Gene Expression Omnibus (GEO) database. The GEO profiles were integrated to obtain differentially expressed genes (DEGs) using the affy package in R software, with |logFC|> 1.5 and adjusted P < 0.05. The DEGs were utilised for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analyses. Hub genes were identified using Cytoscape and enriched for analysis in www.bioinformatics.com.cn. These hub genes were validated in the four aforementioned datasets and M5-induced HaCaT cells using real-time quantitative polymerase chain reaction (RT-qPCR). Results A total of 359 DEGs were identified, which were mostly associated with responses to bacterium, defence responses to other organism, and antimicrobial humoral response. These DEGs were mostly enriched in the steroid hormone biosynthesis pathway, NOD-like receptor signaling pathway, and cytokine-cytokine receptor interaction. PPI network analysis indicated seven genes (CXCL1, ISG15, CXCL10, STAT1, OASL, IFIT1, and IFIT3) as the probable hub genes of psoriasis; CXCL10 had a positive correlation with the other six hub genes. The chord plot results further supported the GO and KEGG analysis results of the 359 DEGs. Seven predicted hub genes were validated to be upregulated in four datasets and M5-induced HaCaT cells using RT-qPCR. Conclusions The pathogenesis of psoriasis may be associated with seven hub genes (CXCL1, ISG15, CXCL10, STAT1, OASL, IFIT1, and IFIT3) and pathways, such as the NOD-like receptor signaling pathway and cytokine-cytokine receptor interaction. These hub genes, especially CXCL10, can be used as potential biomarkers in psoriasis.

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The Mutation of Ednrb(c.857 T > C) Associated With Atrophied Spleen Phenotype in Mice

10.21203/rs.3.rs-229607/v1 ◽

2021 ◽

Author(s):

Fei Wu ◽

Mei Li ◽

Fu-Wen Wang ◽

Yuan Gao ◽

Tariq Munir ◽

...

Keyword(s):

Signaling Pathway ◽

Enrichment Analysis ◽

Signal Pathway ◽

Hippo Signaling ◽

Wild Type ◽

Hippo Signaling Pathway ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway ◽

Upregulated Genes ◽

Small Spleen

Abstract Background:The endothelin signaling pathway plays an important function in the migration, proliferation, and differentiation of neural crest cells. Endothelin receptor B (EDNRB) was reported to have a small spleen phenotype in its deficient mouse model .In our study, we also found that the mutation of EDNRB gene (c. 857 T > c) led to an atrophied spleen phenotype in mice. Different genotypes of EDNRB were significantly correlated with the spleen-kidney ratio, and the spleen phenotypes of Ednrbm1yzcm mice were smaller. The results of the tissue section and H&E staining showed that the spleen microstructure of Ednrbm1yzcm mice was abnormal. In order to explore the molecular mechanism, three groups of Ednrbm1yzcm and wild-type mice were used as control, and standard |log2(FoldChange)|>1 and Padj<0.05 were used to study the influence of EDNRB gene mutation on spleen transcriptional group in mice. GO and KEGG enrichment analysis was conducted to explore the signal pathway related to small spleen phenotype.Results: Through sequencing of mouse spleen transcriptome, 121 differentially expressed genes were selected. Results of the KEGG pathway enrichment analysis showed that in Ednrbm1yzcm mice, upregulated genes were significantly enriched in the Hippo signaling pathway, this pathway inhibits cell growth and modulates organs size and volume; and down-regulation of immune functionally associated pathways such as cytokine receptor interaction and chemokine signaling pathway. In addition, chemokine of Chemokine signaling pathway may also be related to the development of spleen immune tissue structure.Conclusions: In the experiment, we found that mice with mutations in the EDNRB gene have features such as an atrophied spleen and changes in the structure of the spleen. In order to explore the reasons, we performed RNA sequencing on three groups of Edrnrbm1yzcm and wild-type mice, and we found that upregulated genes were significantly enriched in the Hippo signaling pathway. And this signal Pathway is a proven signaling pathway that controls organ size and immune function, so we speculate that the size of the spleen may be related to the Hippo signaling pathway. This study provides a theoretical study of the mechanism of spleen development.

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Bioinformatic analysis of key pathways and genes involved in pediatric atopic dermatitis

Bioscience Reports ◽

10.1042/bsr20193517 ◽

2020 ◽

Author(s):

Tianyi Wang ◽

Bingxin Zhang ◽

Danhui Li ◽

Xiaoli Qi ◽

Chijin Zhang

Keyword(s):

Atopic Dermatitis ◽

Actin Cytoskeleton ◽

Signaling Pathway ◽

Expression Profiles ◽

Receptor Interaction ◽

Interleukin 17 ◽

Hub Genes ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway ◽

Regulation Of Actin Cytoskeleton

The initiation of atopic dermatitis (AD) typically happens very early in life, but most of our understanding of AD is derived from studies on AD patients in adult. The aim of this study was to identify gene signature speficic to pediatric AD comapred to adult AD. The gene expression profiles of four datasets (GSE32924, GSE36842, GSE58558, and GSE107361) were downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network was constructed by Cytoscape software. Total 654 differentially expressed genes (DEGs) (394 up-regulated and 260 down-regulated) were identified in pediatric AD samples with adult AD samples as control. The up-regulated DEGs were significantly enriched in the migration and chemotaxis of granulocyte and neutrophil, while down-regulated DEGs were significantly enriched in biological adhesion. KEGG pathway analysis showed that up-regulated DEGs participated in chemokine signaling pathway while down-regulated DEGs participated in adherens junction, Focal adhesion, Regulation of actin cytoskeleton. The top 10 hub genes, GAPDH, EGFR, ACTB, ESR1, CDK1, CXCL8, CD44, KRAS, PTGS2, SMC3 were involved in chemokine signaling pathway, cytokine-cytokine receptor interaction, interleukin-17 signaling pathway, and regulation of actin cytoskeleton. In conclusion, we identified DEGs and hub genes involved in pediatric AD, which might be used as therapeutic targets and diagnostic biomarkers for pediatric AD.

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Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02464-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Tianye Lin ◽

Weijian Chen ◽

Peng Yang ◽

Ziqi Li ◽

Qiushi Wei ◽

...

Keyword(s):

Femoral Head ◽

Signaling Pathways ◽

Signaling Pathway ◽

Peripheral Blood ◽

Bioinformatics Analysis ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Pathway Enrichment ◽

Qrt Pcr

Abstract Background Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms. Methods Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results. Results A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis. Conclusions The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH.

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Identification of Issue Inhibitor of Metalloproteinase 1 (TIMP1) as a Potential Biomarker for the Diagnosis, Pathogenesis and Prognosis of Colorectal Cancer via Integrated Bioinformatic Analysis

10.21203/rs.3.rs-136189/v1 ◽

2020 ◽

Author(s):

Guona Li ◽

Mengmeng Kang ◽

Siyuan Sheng ◽

Ziyi Chen ◽

Kunshan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Network Analysis ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Molecular Therapy ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Hub Genes ◽

Pathway Enrichment ◽

Potential Biomarker

Abstract Background: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. It is crucial to screen potential biomarkers for the diagnosis, pathogenesis, and prognosis of CRC because there are limited clinical symptoms associated with this cancer. Therefore, we attempted to identify biomarkers associated with the occurrence and progression of CRC by utilizing bioinformatic analysis and to elucidate a molecular mechanism for the diagnosis and treatment of CRC. Methods: Two independent gene expression profile datasets of colonic neoplasms (GSE44076 and GSE37182) were collected from public GEO datasets, which included 182 tumor tissues and 236 normal tissues. Next, differentially expressed genes (DEGs) between CRC colonic samples and non-CRC colonic samples were obtained via GEO2R online tools. Subsequently, hub genes were selected by several analyses of DEGs, including GO pathway enrichment analysis, KEGG pathway enrichment analysis, and PPI network analysis. Finally, the correlation between the hub genes and the occurrence of CRC was tested by harnessing survival analysis and ROC curve analysis. Results: Sixty-one shared DEGs were screened, including 44 high-expression genes and 17 low-expression genes, in CRC samples. Four genes (MYC, TIMP1, MMP7, and COL1A1) were considered to be hub genes because they exhibited higher connectivity degree scores through PPI network analysis. More importantly, there was a significant correlation between increased expression of TIMP1 and reduced survival time in patients with colorectal cancer. Conclusion: By using bioinformatic analysis, this study suggested that Timp-1 may represent a potential biomarker for the diagnosis and prognosis of targeted molecular therapy for CRC.

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