scholarly journals Comprehensive Pan-Cancer Analysis Confirmed That ATG5 Promoted the Maintenance of Tumor Metabolism and the Occurrence of Tumor Immune Escape

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunxiao Xu ◽  
Yusheng Zang ◽  
Yuxiang Zhao ◽  
Weiqiang Cui ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Solid Tumors ◽  
Tumor Immunity ◽  
Immune Checkpoint ◽  
Tumor Metabolism ◽  
Gene Set Enrichment Analysis ◽  
Related Protein ◽  
Tumor Immune Escape ◽  
Pan Cancer

BackgroundAutophagy related protein 5 (ATG5) is an important autophagosome formation related protein, and its involvement in the biological process of autophagy has been shown to correlate with tumor metabolic patterns and the formation of tumor heterogeneity. However, the role of ATG5 in tumor metabolism and tumor immunity remains unclear.MethodIn order to explore this problem, this study was designed to reveal the role of ATG5 in tumor metabolism and tumor immunity through pan-cancer analysis of multi-database. GTEx database, CCLE database, and TCGA database were used to describe the expression, prognosis, immune microenvironment, immune new antigen, immune checkpoint, TMB, and microsatellite instability of ATG5 in 33 types of tumors. A series of bioinformatics tools and methods were used for quantitative analysis and panoramic description, such as to Estimate, Scanneo and GSEA.ResultThe differential analysis results of multiple databases showed that ATG5 was ubiquitously highly expressed in pan-cancer, especially in solid tumors. Survival analysis revealed that ATG5 was universally associated with the prognosis of pan-cancer, and high ATG5 expression was significantly associated with poor patient prognosis in most cases. Further, the expression level of ATG5 was confirmed to be associated with tumor immune infiltration and tumor microenvironment, especially in BRCA, KIRC, and LIHC. In addition to this, ATG5 expression was confirmed to correlate with these clinically significant phenotypes, in conjunction with immune neoantigens and immune checkpoint gene expression profiles in pan-cancer. In addition to TMB and microsatellite instability in pan-cancer, we confirmed that ATG5 expression affects the expression of DNA repair genes and methyltransferases in pan-cancer, and found through gene set enrichment analysis that ATG5 is involved in the regulation of numerous signaling pathways involved in cancer metabolism and cancer immunity.ConclusionsATG5 participated in the formation of autophagosomal membrane important molecule LC3-II outside, and played an important role in tumor metabolism and tumor immunity. The comprehensive pan-cancer analysis not only revealed the potential of ATG5 in tumor-targeted therapy but also suggested ATG5 as a promising tumor predictive biomarker in most solid tumors.

scholarly journals Prognostic and immunological role of Ras-related protein Rap1b in pan-cancer

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4828-4840
Author(s):  
Guoliang Cui ◽  
Can Wang ◽  
Zhenyan Lin ◽  
Xiaoke Feng ◽  
Muxin Wei ◽  
...  
Keyword(s):  
Related Protein ◽  
Pan Cancer

scholarly journals Aggresome–Autophagy Associated Gene HDAC6 Is a Potential Biomarker in Pan-Cancer, Especially in Colon Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiyong Zhang ◽  
Xin Zhang ◽  
Aimin Huang
Keyword(s):  
Expression Profiles ◽  
Cancer Cell Line ◽  
Tumor Metabolism ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
Histone Deacetylase 6 ◽  
Potential Biomarker ◽  
Pan Cancer

BackgroundHistone deacetylase 6 (HDAC6) regulates cytoplasmic signaling networks through the deacetylation of various cytoplasmic substrates. Recent studies have identified the role of HDAC6 in tumor development and immune metabolism, but its specific function remains unclear.MethodsThe current study determined the role of HDAC6 in tumor metabolism and tumor immunity through a multi-database pan-cancer analysis. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the expression levels, prognosis, tumor progression, immune checkpoints, and immune metabolism of HDAC6 in 33 tumors. Pathways, immune checkpoints, immune neoantigens, immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), DNA mismatch repair (MMR), and the value of methyltransferases. The R package was used for quantitative analysis and panoramic description.ResultsIn the present study, we determined that HDAC6 is differentially expressed in pan carcinomas, and by survival, we found that HDAC6 was generally associated with the prognosis of pancreatic adenocarcinoma, Thymoma, and uveal melanoma, where low expression of HDAC6 had a significantly worse prognosis. Secondly, through this experiment, we confirmed that HDAC6 expression level was associated with tumor immune infiltration and tumor microenvironment, especially in PAAD. Finally, HDAC6 was associated with immune neoantigen and immune checkpoint gene expression profiles in all cancers in addition to TMB and MSI in pan-cancers.ConclusionHDAC6 is differentially expressed in pan-cancers and plays an essential role in tumor metabolism and immunity. HDAC6 holds promise as a tumor potential prognostic marker, especially in colon cancer.

scholarly journals Immune infiltration of MMP14 in Pan-cancer and its prognostic effect on tumor

2021 ◽  
Author(s):  
Minde Li ◽  
Shaoyang Li ◽  
Lin Zhou ◽  
Le Yang ◽  
Xiao Wu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Mutation Load ◽  
Immune Infiltration ◽  
Tumor Prognosis ◽  
Checkpoint Genes ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: Matrix metallopeptidase 14(MMPL4) is a member of the matrix metalloproteinase family, which interacts with tissue metalloproteinase inhibitors (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 on pan-cancer. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Methods: In this study, we used bioinformatics to analyze data from multiple databases, including TCGA, Oncomine and Kaplan-Meier Plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Results: MMP14 expression is highly associated with prognosis of a variety of cancers, tumor immunoinvasion, and has important effects on pan-oncologic mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes. Conclusion: MMP14 is highly correlated with tumor prognosis and immunoinvasion, and affects the occurrence and progression of many tumors. All these fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis and treatment of many tumors, and provide a new idea and direction for subsequent tumor immune research and treatment strategies.

scholarly journals Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Da Huang ◽  
Jiayu Shen ◽  
Lingyun Zhai ◽  
Huanhuan Chen ◽  
Jing Fei ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Tumor Immunity ◽  
Malignant Tumors ◽  
Physiological Role ◽  
Cancer Cell Line ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

Effect of CCND1 amplification on immunosuppression and the association with a poor prognosis to immune checkpoint inhibitors in solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15249-e15249 ◽  
Author(s):  
Yingying Huang ◽  
Chuan-ben Chen ◽  
Yu Chen ◽  
Xuan Gao ◽  
Yi Li ◽  
...  
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gene Set Enrichment Analysis ◽  
Biological Behavior ◽  
Cancer Center ◽  
Mesenchymal Transition ◽  
Ccnd1 Amplification

e15249 Background: CCND1 amplification relevant to malignant biological behavior exist in solid tumors. The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown. Methods: This study included three cohorts: Geneplus Institute ( n= 6536), The Cancer Genome Atlas ( n= 10562) and Memorial Sloan Kettering Cancer Center ( n= 106109). Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and their correlation with the prognosis and the response to ICIs. Results: CCND1 amplification occurs in many cancer types, correlates with shorter overall survival and inferior outcomes with ICIs therapy. Transcriptomic analysis showed various degrees of immune cells exclusion, including cytotoxic cells, T cells, CD8+ T cells, DC cells, B cells in the tumor microenvironment (TME) in a CCND1 amplification population. The gene set enrichment analysis suggested that CCND1 amplification correlates with multiple aggressive, immunosuppressive hallmarks including epithelial mesenchymal transition, TGF-β signaling, KRAS signaling, PI3K/AKT/mTOR signaling, p53 pathway and hypoxia signaling in solid tumors. Conclusions: Our study indicated that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs in solid tumors.

scholarly journals Emerging role of SWI/SNF complex deficiency as a target of immune checkpoint blockade in human cancers

Oncogenesis ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Min Zhou ◽  
Jianlong Yuan ◽  
Yaqi Deng ◽  
Xianqun Fan ◽  
Jianfeng Shen
Keyword(s):  
Tumor Immunity ◽  
Immune Checkpoint ◽  
Cancer Therapeutics ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Human Cancers ◽  
Complex Deficiency ◽  
Specific Vulnerability ◽  
Underlying Mechanisms

AbstractMammalian SWI/SNF complex is a key chromatin remodeler that reshapes nucleosomes and regulates DNA accessibility. Mutations in SWI/SNF subunits are found in a broad spectrum of human cancers; however, the mechanisms of how these aberrations of SWI/SNF complex would impact tumorigenesis and cancer therapeutics remain to be elucidated. Studies have demonstrated that immune checkpoint blockade (ICB) therapy is promising in cancer treatment. Nevertheless, suitable biomarkers that reliably predict the clinical response to ICB are still lacking. Emerging evidence has suggested that SWI/SNF components play novel roles in the regulation of anti-tumor immunity, and SWI/SNF deficiency can be therapeutically targeted by ICB. These findings manifest the prominence of the SWI/SNF complex as a stratification biomarker that predicts treatment (therapeutic) response to ICB. In this review, we summarize the recent advances in ICB therapy by harnessing the cancer-specific vulnerability elicited by SWI/SNF deficiency. We provide novel insights into a comprehensive understanding of the underlying mechanisms by which SWI/SNF functions as a modulator of anti-tumor immunity.

scholarly journals Pan-Cancer Analysis Reveals RIPK2 Predicts Prognosis and Promotes Immune Therapy Resistance Via Triggering Cytotoxic T Lymphocytes Dysfunction

2021 ◽  
Author(s):  
junquan song ◽  
Runyu Yang ◽  
Rongyuan Wei ◽  
Yue Du ◽  
Pengcheng He ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Immune Checkpoint ◽  
Immune Therapy ◽  
Therapy Resistance ◽  
High Expression ◽  
Expression Level ◽  
Immune Score ◽  
Pan Cancer

Abstract Background Receptor-interacting protein kinase 2 (RIPK2, also known as RIP2) was reported to be associated with bacterial infections as well as inflammatory responses. However, the role of RIPK2 in prognosis and immunotherapy response is yet to be elucidated in human pan-cancer. Methods In this study, we investigated the expression, gene alteration landscape and prognostic value of RIPK2 in 33 cancers through various databases including Ualcan, cBioportal and GEPIA. Then, the correlation between RIPK2 and immune infiltration, immune score, stromal score, and ESTIMATE score was investigated in the TGGA and TIMER database. Independent cohorts were utilized to explore the role of RIPK2 in tumor immunotherapy response. Furthermore, GSEA analysis was conducted to explore the mechanisms by which RIPK2 regulates immune therapy resistance. Single-cell RNA-seq datasets were used to analyze the expression level of RIPK2 on different immune cells. Moreover, CellMiner database was used to explore the relationship between RIPK2 expression with drug response. Result Compared with normal tissue, tumor tissue had a higher expression level of RIPK2 in various cancers. Survival analysis showed that high expression of RIPK2 associated with poor prognosis in numerous cancers. RIPK2 was found to promote a series of immune cell infiltration and B cells, macrophages, and neutrophils were significantly positively correlated with the expression of RIPK2. Moreover, RIPK2 affected immune score, stromal score and ESTIMATE score for a wide range of cancers. In the vast majority of 33 cancers, gene co-expression analysis showed that RIPK2 was positively correlated with the expression of immune checkpoint markers, such as PDCD1 (PD-1), CD274 (PD-L1), CTLA4 and TIGIT. RIPK2 aggravated cytotoxic T lymphocyte (CTL) dysfunction and related to the poor efficacy of immune checkpoint blockade in skin cutaneous melanoma (SKCM) and kidney renal clear cell carcinoma (KIRC). High expression of RIPK2 promoted innate immunotherapy resistance and adaptive immunotherapy resistance through IL-6/JAK/STAT3 signaling, interferon-gamma response, and interferon-alpha response pathway. Conclusion These results confirmed that RIPK2 could serve as a prognostic biomarker and promoted immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.

scholarly journals The Role of M6A-related CBLL1 in the Prognosis and Immune Infiltration of Pan-cancer

2020 ◽  
Author(s):  
Qiang Guo ◽  
Dan Li ◽  
Yan-Mei Ji ◽  
Jialong Guo
Keyword(s):  
Mrna Expression ◽  
Immune Cells ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Cycle Phase ◽  
Immune Infiltration ◽  
The Relationship ◽  
Pan Cancer ◽  
Ucsc Database

Abstract Background The modification of N6-methyladenosine (m6A) plays an important role in physiology and disease progression. The relationship between the role of m6a-related gene CBLL1 in pan-carcinoma and tumor immune infiltrates has remained unknown. Methods To explore the expression level of CBLL1 methylation in pan-cancer in SMART database, and download mRNA expression, mutation and clinical data in UCSC database, to analyze the expression level of CBLL1, and the relationship between CBLL1 expression and clinicopathological features, prognosis, mutation and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between the expression of CBLL1 and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. Gene Set enrichment analysis (GSEA) revealed the possible mechanism of CBLL1 in the regulation of pan-cancer progression. Results The levels of CBLL1 methylation and mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM.The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden (TMB), and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability (MSI). The expression level of CBLL1 was correlated with pan-cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. GSEA found that CBLL1 may participate in the progression of pan-cancer through B cell receptor singaling pathway, mRNA binding, immunoglobulin receptor binding, Positive Regulation of cell cycle phase transition and other mechanisms. Conclusions CBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.

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