Analyzing the Impact of ATF3 in Tumorigenesis and Immune Cell Infiltration of Ovarian Tumor: A Bioinformatics Study

Cell Infiltration ◽

Transcription Activator ◽

Critical Pathways ◽

Abstract ATF3 is an essential transcription activator in regulating cancer-related genetic expression. To identify the role of ATF3 in ovarian, we investigated the correlation between ATF3 expression and the clinicopathological properties using multiple database. The cBioPortal and GEPIA database displayed the clinical information of ovarian patients harboring or without harboring ATF3 mutation. Furthermore, we assessed the relationship between survival and ATF3 expression level using Kaplan-Meier plotter, which reveals that the ovarian patients with higher expression of ATF3 suffered the worse overall survival and progression-free survival. The differentially expressed genes were analyzed using Gene Ontology, protein-protein interaction network and gene set enrichment analysis to identify the hub gene and critical pathways, significantly affecting the tumorigenesis of ovarian tumor. Finally, we assessed the correlation between ATF3 and immune cell infiltration using Tumor Immunoassay Resource (TIMER) database. The results demonstrated that higher expression is positive correlation with macrophage infiltration, expression for M1 and M2 type macrophages. Our study suggests that ATF3 can regulate the cell cycle and heme-related oxidative phosphorylation process, and it may be a critical factor to regulate the macrophage cell to be infiltrated into ovarian cancer. ATF3 can be as a biomarker for diagnosis and therapy of ovarian.

Identification of Methylated Differentially Expressed Hub Genes and Immune Infiltration in Diabetic Retinopathy

10.21203/rs.3.rs-1136469/v1 ◽

2021 ◽

Author(s):

Qi Zhou ◽

Xin Xiong ◽

Min Tang ◽

Yingqing Lei ◽

Hongbin Lv

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Immune Cell ◽

Interaction Network ◽

Bioinformatic Analysis ◽

Differentially Expressed ◽

Cell Infiltration ◽

Hub Genes ◽

Critical Pathways

Abstract BackgroundDiabetic retinopathy (DR), a severe complication of diabetes mellitus (DM), is a global social and economic burden. However, the pathological mechanisms mediating DR are not well-understood. This study aimed to identify differentially methylated and differentially expressed hub genes (DMGs and DEGs, respectively) and associated signaling pathways, and to evaluate immune cell infiltration involved in DR. MethodsTwo publicly available datasets were downloaded from the Gene Expression Omnibus database. Transcriptome and epigenome microarray data and multi-component weighted gene coexpression network analysis (WGCNA) were utilized to determine hub genes within DR. One dataset was utilized to screen DEGs and to further explore their potential biological functions using functional annotation analysis. A protein-protein interaction network was constructed. Gene set enrichment and variation analyses (GSVA and GSEA, respectively) were utilized to identify the potential mechanisms mediating the function of hub genes in DR. Infiltrating immune cells were evaluated in one dataset using CIBERSORT. The Connectivity Map (CMap) database was used to predict potential therapeutic agents. ResultsIn total, 673 DEGs (151 upregulated and 522 downregulated genes) were detected. Gene expression was significantly enriched in the extracellular matrix and sensory organ development, extracellular matrix organization, and glial cell differentiation pathways. Through WGCNA, one module was found to be significantly related with DR (r=0.34, P =0.002), and 979 hub genes were identified. By comparing DMGs, DEGs, and genes in WGCNA, we identified eight hub genes in DR ( AKAP13, BOC, ACSS1, ARNT2, TGFB2, LHFPL2, GFPT2, TNFRSF1A ), which were significantly enriched in critical pathways involving coagulation, angiogenesis, TGF-β, and TNF-α-NF-κB signaling via GSVA and GSEA. Immune cell infiltration analysis revealed that activated natural killer cells, M0 macrophages, resting mast cells, and CD8 + T cells may be involved in DR. ARNT2, TGFB2, LHFPL2 , and AKAP13 expression were correlated with immune cell processes, and ZG-10, JNK-9L, chromomycin-a3, and calyculin were identified as potential drugs against DR. Finally, TNFRSF1A , GFPT2 , and LHFPL2 expression levels were consistent with the bioinformatic analysis. ConclusionsOur results are informative with respect to correlations between differentially methylated and expressed hub genes and immune cell infiltration in DR, providing new insight towards DR drug development and treatment.

Analyzing the impact of ATF3 in tumorigenesis and immune cell infiltration of ovarian tumor: a bioinformatics study

Medical Oncology ◽

10.1007/s12032-021-01541-7 ◽

2021 ◽

Vol 38 (8) ◽

Author(s):

Xiaoliu Li ◽

Panpan Liu ◽

Xiaona Sun ◽

Runhong Ma ◽

Ting Cui ◽

...

Keyword(s):

Ovarian Tumor ◽

Immune Cell ◽

Cell Infiltration ◽

Bioinformatics Study ◽

Bioinformatics Analysis of C3 in Brain Low Grade Gliomas as Potential Therapeutic Target and Promoting Immune Cell Infiltration

10.21203/rs.3.rs-1040002/v1 ◽

2021 ◽

Author(s):

Xiujuan wu ◽

Siyi Wu ◽

Kaiting Miao ◽

Lijing Wang ◽

Yuanyuan Ma

Keyword(s):

Cell Cycle ◽

Immune Cell ◽

Cell Infiltration ◽

Low Grade ◽

Mesenchymal Transition ◽

Low Grade Gliomas ◽

Regulation Of Cell Cycle ◽

Abstract Background Low grade gliomas is the malignant nervous tumor with distinct biological and clinical characteristics. Despite advances in diagnostic and therapeutic methods, how to significantly elongate the survival of low grade gliomas is still the challenge. Complement 3, as the critical component in the innate immune system, play an essential role in local immune response and participated into the regulation of the epithelial-mesenchymal transition and tumor microenvironment. Methods In this study, we systematically determined the expression levels of C3 in low grade gliomas using various public databases. Then, we further identified the impact of C3 expression on immune cell infiltration compared to normal tissue, indicating the effect of cellular microenvironment on overall survival of LGG patients. Results We obtained transcriptional and survival of C3 in LGG from GEPIA and cBioportal database, and the differentially expressed genes were obtained. By performing the analysis of GO and protein-protein interaction network, we have identified the top-ranked 10 hub genes, which are highly associated with regulation of cell cycle. The gene set enrichment analysis demonstrated that overexpression of C3 in LGG patient is positively correlated with regulation of cell cycle. Finally, the immune cell infiltration of C3 in LGG patients was employed and clearly showed that higher neutrophil infiltration can worsen the survival of LGG patients with higher C3 expression. These results were confirmed by the Human Protein Atlas database, in which expression level of C3 protein in gliomas patients always higher. Conclusions This investigation implied that C3 can be as the potential targets of precise therapy for patient with low grade gliomas.

Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis

Journal of Translational Medicine ◽

10.1186/s12967-020-02698-x ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Xingwang Zhao ◽

Longlong Zhang ◽

Juan Wang ◽

Min Zhang ◽

Zhiqiang Song ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Immune Cell ◽

Expression Profiles ◽

Cell Infiltration ◽

Tissue Destruction ◽

Systemic Lupus ◽

Ppi Networks

Abstract Background Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE is characterized by autoimmune, inflammatory processes, and tissue destruction. Some seriously-ill patients could develop into lupus nephritis. However, the cause and underlying molecular events of SLE needs to be further resolved. Methods The expression profiles of GSE144390, GSE4588, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between SLE and healthy samples. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by metascape etc. online analyses. The protein–protein interaction (PPI) networks of the DEGs were constructed by GENEMANIA software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the functions of the hub gene, Weighted gene co‐expression network analysis (WGCNA) would be utilized to build a gene co‐expression network, and the most significant module and hub genes was identified. CIBERSORT tools have facilitated the analysis of immune cell infiltration patterns of diseases. The receiver operating characteristic (ROC) analyses were conducted to explore the value of DEGs for SLE diagnosis. Results In total, 6 DEGs (IFI27, IFI44, IFI44L, IFI6, EPSTI1 and OAS1) were screened, Biological functions analysis identified key related pathways, gene modules and co‐expression networks in SLE. IFI27 may be closely correlated with the occurrence of SLE. We found that an increased infiltration of moncytes, while NK cells resting infiltrated less may be related to the occurrence of SLE. Conclusion IFI27 may be closely related pathogenesis of SLE, and represents a new candidate molecular marker of the occurrence and progression of SLE. Moreover immune cell infiltration plays important role in the progession of SLE.

Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804506115 ◽

2018 ◽

Vol 115 (50) ◽

pp. E11701-E11710 ◽

Cited By ~ 42

Author(s):

Yoong Wearn Lim ◽

Haiyin Chen-Harris ◽

Oleg Mayba ◽

Steve Lianoglou ◽

Arthur Wuster ◽

...

Keyword(s):

Gene Expression ◽

Cancer Immunotherapy ◽

Genetic Variants ◽

Immune Cell ◽

Response To Therapy ◽

Cell Infiltration ◽

Cancer Type ◽

Durable Response ◽

Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie their differential response to immunotherapy. Herein, we systematically determined the association of common germline genetic variants with gene expression and immune cell infiltration of the tumor. We identified 64,094 expression quantitative trait loci (eQTLs) that associated with 18,210 genes (eGenes) across 24 human cancers. Overall, eGenes were enriched for their being involved in immune processes, suggesting that expression of immune genes can be shaped by hereditary genetic variants. We identified the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene as a pan-cancer type eGene whose expression levels stratified overall survival in a subset of patients with bladder cancer receiving anti–PD-L1 (atezolizumab) therapy. Finally, we identified 103 gene signature QTLs (gsQTLs) that were associated with predicted immune cell abundance within the tumor microenvironment. Our findings highlight the impact of germline SNPs on cancer-immune phenotypes and response to therapy; and these analyses provide a resource for integration of germline genetics as a component of personalized cancer immunotherapy.

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma

PeerJ ◽

10.7717/peerj.12304 ◽

2021 ◽

Vol 9 ◽

pp. e12304

Author(s):

Zhengyuan Wu ◽

Leilei Chen ◽

Chaojie Jin ◽

Jing Xu ◽

Xingqun Zhang ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Immune Status ◽

Immune Cell ◽

Gene Signature ◽

Cell Infiltration ◽

Tumor Cell Death ◽

Prognostic Gene ◽

Prognostic Gene Signature

Background Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. Methods Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. Results Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.

Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.611058 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhuomao Mo ◽

Daiyuan Liu ◽

Dade Rong ◽

Shijun Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Cell ◽

Cox Regression ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Checkpoints ◽

Immunosuppressive Microenvironment

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽

10.1186/s12885-021-08536-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shaokun Wang ◽

Li Pang ◽

Zuolong Liu ◽

Xiangwei Meng

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Immune Cells ◽

Immune Cell ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis

10.21203/rs.2.12276/v1 ◽

2019 ◽

Author(s):

Yiling Cao ◽

Weihao Tang ◽

Wanxin Tang

Keyword(s):

Gene Expression ◽

Lupus Nephritis ◽

Molecular Mechanisms ◽

Immune Cell ◽

Expression Profiles ◽

Cell Infiltration ◽

Spearman Correlation ◽

Core Genes

Abstract Objects Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN. Methods Datasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues of living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Result Five types of immune cells revealed important associations with LN, and monocytes emerged to be the prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features. Conclusion This study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.

KRT17 Serves as an Oncogene and a Predictor of Poor Survival in Hepatocellular Carcinoma Patients

10.21203/rs.3.rs-117723/v1 ◽

2020 ◽

Author(s):

yuyan chen ◽

Jing Chen ◽

Zu-Cheng Tian ◽

Dan-Hua Zhou ◽

Ran Ji ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Cell ◽

Immune Cell ◽

Cell Infiltration ◽

Cancer Type ◽

Functional Link ◽

Network Analyses ◽

Ppi Networks

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cancer-associated cause of death globally. It is thus vital that novel diagnostic and prognostic biomarkers associated with early-stage HCC be identified. While keratin 17 (KRT17) has previously been reported to be associated with certain cancer types, its relationship with HCC remains to be defined. Methods：The expression of KRT17 in the TCGA LIHC database and in 44 pairs of HCC patient samples was assessed via qRT-PCR, western blotting, and immunohistochemical staining. The prognostic relevance of KRT17 was assessed using Kaplan-Meir curves, while important cancer- and KRT17-related biological processes were defined through gene set enrichment analysis (GSEA). The functional link between KRT17 expression and tumor cell proliferation/survival was assessed through flow cytometry, colony formation assay, CCK-8 assay, and subcutaneous tumor model approaches. Protein-protein interaction (PPI) networks and analyses of immune cell infiltration were also employed to define key signaling pathways associated with KRT17 expression in HCC. Results：HCC tissue samples exhibited increased KRT17 mRNA and protein expression that was predictive of poorer patient survival (P<0.001). GSEA and functional experiments revealed that KRT17 functioned as a regulator of HCC tumor cell survival, proliferation, and cell cycle progression in vitro and in vivo. PPI network analyses also revealed that KRT17 expression was linked to immune cell infiltration and activation in patients with HCC. Conclusion: We found that increased KRT17 levels were associated with poorer survival, more aggressive disease, and altered immune cell infiltration in patients suffering from HCC. As such, KRT17 may function as an oncogene and a prognostic biomarker in this cancer type.