scholarly journals Characteristics of immune cell infiltration and associated diagnostic biomarkers in ulcerative colitis: results from bioinformatics analysis

Bioengineered ◽  
2020 ◽  
Author(s):  
Guohui Xue ◽  
Lin Hua ◽  
Nanjin Zhou ◽  
Junming Li
Keyword(s):  
Ulcerative Colitis ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Diagnostic Biomarkers

Integrated Bioinformatics Analysis of Differentially-Expressed Genes and Immune Cell Infiltration Characteristics in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Zitong Feng ◽  
Jingge Qu ◽  
Xiao Liu ◽  
Jinghui Liang ◽  
Yongmeng Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a significant challenge. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identified by the “limma” R package, and a total of 152 robust DEGs were identified by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were significantly associated with extracellular matrix related process. Immune cell infiltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC.

scholarly journals Identification of key genes involved in tumor immune cell infiltration and cetuximab resistance in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Liang ◽  
Mengling Liu ◽  
Xun Sun ◽  
Yitao Yuan ◽  
Ke Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Cellular Model ◽  
Gene Set

Abstract Background The anti-epidermal growth factor receptor (EGFR) antibody introduces adaptable variations to the transcriptome and triggers tumor immune infiltration, resulting in colorectal cancer (CRC) treatment resistance. We intended to identify genes that play essential roles in cetuximab resistance and tumor immune cell infiltration. Methods A cetuximab-resistant CACO2 cellular model was established, and its transcriptome variations were detected by microarray. Meanwhile, public data from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database were downloaded. Integrated bioinformatics analysis was applied to detect differentially expressed genes (DEGs) between the cetuximab-resistant and the cetuximab-sensitive groups. Then, we investigated correlations between DEGs and immune cell infiltration. The DEGs from bioinformatics analysis were further validated in vitro and in clinical samples. Results We identified 732 upregulated and 1259 downregulated DEGs in the induced cellular model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, along with Gene Set Enrichment Analysis and Gene Set Variation Analysis, indicated the functions of the DEGs. Together with GSE59857 and GSE5841, 12 common DEGs (SATB-2, AKR1B10, ADH1A, ADH1C, MYB, ATP10B, CDX-2, FAR2, EPHB2, SLC26A3, ORP-1, VAV3) were identified and their predictive values of cetuximab treatment were validated in GSE56386. In online Genomics of Drug Sensitivity in Cancer (GDSC) database, nine of twelve DEGs were recognized in the protein-protein (PPI) network. Based on the transcriptome profiles of CRC samples in TCGA and using Tumor Immune Estimation Resource Version 2.0, we bioinformatically determined that SATB-2, ORP-1, MYB, and CDX-2 expressions were associated with intensive infiltration of B cell, CD4+ T cell, CD8+ T cell and macrophage, which was then validated the correlation in clinical samples by immunohistochemistry. We found that SATB-2, ORP-1, MYB, and CDX-2 were downregulated in vitro with cetuximab treatment. Clinically, patients with advanced CRC and high ORP-1 expression exhibited a longer progression-free survival time when they were treated with anti-EGFR therapy than those with low ORP-1 expression. Conclusions SATB-2, ORP-1, MYB, and CDX-2 were related to cetuximab sensitivity as well as enhanced tumor immune cell infiltration in patients with CRC.

scholarly journals POS0363 IDENTIFICATION OF MOLECULAR PHENOTYPES AND IMMUNE CELL INFILTRATION IN PSORIATIC ARTHRITIS PATIENTS’ SKIN TISSUES BY INTEGRATED BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 411.1-411
Author(s):  
T. Cheng ◽  
S. X. Zhang ◽  
J. Qiao ◽  
R. Zhao ◽  
S. Song ◽  
...  
Keyword(s):  
T Cells ◽  
Psoriatic Arthritis ◽  
Nk Cells ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Signature Genes ◽  
Molecular Phenotypes

Background:Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease associated with cutaneous psoriasis1. Heterogeneity of clinical manifestation often makes differential diagnosis difficult 2. Thus, the underlying molecular pathogenesis of PsA need to be further studied to diagnose early and ensure optimal management of arthritis and key comorbidities.Objectives:This research was conducted to identify molecular phenotypes and immune infiltration in the skin tissues of psoriatic arthritis patients according to bioinformatics analysis.Methods:The mRNA expression profiles of GSE13355 (116 samples), GSE14905 (56 samples) and GSE30999 (162 samples) were obtained from the publicly GEO databases. Non-negative matrix factorization (NMF), functional enrichment and cibersort algorithm were applied to illustrate the conditions of PsA patients’ skin tissues for classification after screening the differentially expressed genes (DEGs) between lesion biopsy and non-lesion biopsy.Results:Two subsets (Sub1 and Sub2) were identified and validated by NMF typing of 612 detected DEGs (Figure 1a). A total of 54 signature genes (18 in Sub1 and 36 in Sub2) were obtained (Figure 1b). GO and KEGG enrichment analysis showed the signature genes in Sub1 were mainly involved in proliferation and differentiation of immune cells, whereas genes in Sub2 were related to humoral immune response mediated by antimicrobial peptide (Figure 1c.1d). Further, immune cell infiltration results revealed Sub2 had higher levels of resting NK cells (P<0.001), macrophages M1(P<0.001), resting mast cells (P<0.001) and regulatory T cells (P<0.001) but lower concentrations of activated CD4+ memory T cells (P<0.001), activated NK cells (P<0.05), activated dendritric cells(P<0.001), eosinophils (P<0.05) and neutrophil (P<0.001) (Figure 1e).Conclusion:The pathogenesis of psoriatic arthritis is related to both cellular immunity and humoral immunity. It is indispensable to adjust the treatment strategies according to patient’s immune status.References:[1]Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. The New England journal of medicine 2017;376(10):957-70. doi: 10.1056/NEJMra1505557 [published Online First: 2017/03/09].[2]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet (London, England) 2018;391(10136):2273-84. doi: 10.1016/s0140-6736(18)30830-4 [published Online First: 2018/06/13].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals TMC5 is Highly Expressed in Human Cancers and Corelates to Prognosis and Immune Cell Infiltration: A Comprehensive Bioinformatics Analysis

2022 ◽  
Vol 8 ◽  
Author(s):  
Hui Zhang ◽  
Xu Zhang ◽  
Weiguo Xu ◽  
Jian Wang
Keyword(s):  
Tumor Tissue ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Drug Responses ◽  
Normal Tissues ◽  
Human Cancers ◽  
Potential Marker ◽  
Pathological Stages

Background: The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis.Methods: With reference to the accessible online databases, the TMC5 expressions in tumor tissues and corresponding normal tissues, different pathological stages, and various cancer cells were analyzed, while the protein levels of TMC5 in different cancers were also inspected. Meanwhile, the prognostic value of TMC5 expression in multiple cancers as well as in advanced-stage patients was investigated. Furthermore, the mutational data of TMC5 and its correlation with cancer prognosis were assessed. Moreover, the association between the TMC5 level and immune cell infiltration was evaluated. Next, TMC5-related pathway alterations and drug responses were summarized. Finally, the TMC5 based protein network was generated, and relevant enrichment was performed.Results: In our study, the expression level of TMC5 was significantly higher in the tumor tissue than that of the normal tissues in most cancer types. Fluctuations of TMC5 levels were also observed among different pathological stages. In the meantime, the protein level elevated in the tumor tissue in the cancers enrolled. Moreover, the expression of TMC5 was not only prognostic for overall survival (OS) or recurrence free survival (RFS) in various types of cancers but also correlated to OS in patients with more advanced cancers. Additionally, the mutational status of TMC5 is also associated with prognosis in cancer patients. It is worth noting that the TMC5 level was closely related to immune cell infiltrations, especially in ESCA, TGCT, and USC. The TMC5 expression was also identified as an activator for pathways including PI3K/AKT, RAS/MAPK, and TSC/mTOR, proved to be associated with multiple drug responses and assessed to be interactive with the TMEM family.Conclusion: TMC5 might function as a potential marker for cancer survival and immune responses.

scholarly journals Identification of Disease-Specific Hub Biomarkers and Immune Infiltration in Osteoarthritis and Rheumatoid Arthritis Synovial Tissues by Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Fei Sun ◽  
Jian lin Zhou ◽  
Pu ji Peng ◽  
Chen Qiu ◽  
Jia rui Cao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Relative Proportion ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Synovial Tissues ◽  
Disease Specific

Background. Osteoarthritis (OA) and rheumatoid arthritis (RA) are well-known cause of joint disability. Although they have shown the analogous clinical features involving chronic synovitis that progresses to cartilage and bone destruction, the pathogenesis that initiates and perpetuates synovial lesions between RA and OA remains elusive. Objective. This study is aimed at identifying disease-specific hub genes, exploring immune cell infiltration, and elucidating the underlying mechanisms associated with RA and OA synovial lesion. Methods. Gene expression profiles (GSE55235, GSE55457, GSE55584, and GSE12021) were selected from Gene Expression Omnibus for analysis. Differentially expressed genes (DEGs) were identified by the “LIMMA” package in Bioconductor. The DEGs were identified by Gene Ontology (GO) and KEGG pathway analysis. A protein-protein interaction network was constructed to identify candidate hub genes by using STRING and Cytoscape. Hub genes were identified by validating from GSE12021. Furthermore, we employed the CIBERSORT website to assess immune cell infiltration between OA and RA. Finally, we explored the correlation between the levels of hub genes and relative proportion of immune cells in OA and RA. Results. We identified 68 DEGs which were mainly enriched in immune response and chemokine signaling pathway. Six hub genes with a cutoff of AUC > 0.80 by ROC analysis and relative expression of P < 0.05 were identified successfully. Compared with OA, the RA synovial tissues consisted of a higher proportion of 7 immune cells, whereas 4 immune cells were found in relatively lower proportion ( P < 0.05 ). In addition, the levels of 6 hub genes were closely associated with relative proportion of 11 immune cells in OA and RA. Conclusions. We used bioinformatics analysis to identify hub genes and explored immune cell infiltration of immune microenvironment in synovial tissues. Our results should offer insights into the underlying molecular mechanisms of synovial lesion and provide potential target for immune-based therapies of OA and RA.

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