scholarly journals m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Fei Liu ◽  
Xiaopeng Yu ◽  
Guijin He
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Genomic Variation ◽  
Gene Set Enrichment Analysis ◽  
Single Sample ◽  
Gene Set Enrichment ◽  
Gene Set

Background. We analyzed the n6-methyladenosine (m6A) modification patterns of immune cells infiltrating the tumor microenvironment of breast cancer (BC) to provide a new perspective for the early diagnosis and treatment of BC. Methods. Based on 23 m6A regulatory factors, we identified m6A-related gene characteristics and m6A modification patterns in BC through unsupervised cluster analysis. To examine the differences in biological processes among various m6A modification modes, we performed genomic variation analysis. We then quantified the relative infiltration levels of different immune cell subpopulations in the tumor microenvironment of BC using the CIBERSORT algorithm and single-sample gene set enrichment analysis. Univariate Cox analysis was used to screen for m6A characteristic genes related to prognosis. Finally, we evaluated the m6A modification pattern of patients with a single BC by constructing the m6Ascore based on principal component analysis. Results. We identified three different m6A modification patterns in 2128 BC samples. A higher abundance of the immune infiltration of the m6Acluster C was indicated by the results of CIBERSORT and the single-sample gene set enrichment analysis. Based on the m6A characteristic genes obtained through screening, the m6Ascore was determined. The BC patients were segregated into m6Ascore groups of low and high categories, which revealed significant survival benefits among patients with low m6Ascores. Additionally, the high-m6Ascore group had a higher mutation frequency and was associated with low PD-L1 expression, and the m6Ascore and tumor mutation burden showed a positive correlation. In addition, treatment effects were better in patients in the high-m6Ascore group. Conclusions. In case of a single patient with BC, the immune cell infiltration characteristics of the tumor microenvironment and the m6A methylation modification pattern could be evaluated using the m6Ascore. Our results provide a foundation for improving personalized immunotherapy of BC.

scholarly journals PVT1 is a prognostic marker associated with immune invasion of bladder urothelial carcinoma

2021 ◽  
Vol 19 (1) ◽  
pp. 169-190
Author(s):  
Peiyuan Li ◽  
◽  
Gangjie Qiao ◽  
Jian Lu ◽  
Wenbin Ji ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Gene Set Enrichment ◽  
Cox Regression Analysis ◽  
Gene Set ◽  
Bladder Urothelial Carcinoma

<abstract> <p>Plasmacytoma variant translocation 1 (PVT1) is involved in multiple signaling pathways and plays an important regulatory role in a variety of malignant tumors. However, its role in the prognosis and immune invasion of bladder urothelial carcinoma (BLCA) remains unclear. This study investigated the expression of PVT1 in tumor tissue and its relationship with immune invasion, and determined its prognostic role in patients with BLCA. Patients were identified from the cancer genome atlas (TCGA). The enrichment pathway and function of PVT1 were explained by gene ontology (GO) term analysis, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA), and the degree of immune cell infiltration was quantified. Kaplan–Meier analysis and Cox regression were used to analyze the correlation between PVT1 and survival rate. PVT1-high BLCA patients had a lower 10-year disease-specific survival (DSS P &lt; 0.05) and overall survival (OS P &lt; 0.05). Multivariate Cox regression analysis showed that PVT1 (high vs. low) (P = 0.004) was an independent prognostic factor. A nomogram was used to predict the effect of PVT1 on the prognosis. PVT1 plays an important role in the progression and prognosis of BLCA and can be used as a medium biomarker to predict survival after cystectomy.</p> </abstract>

scholarly journals Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingbo Sun ◽  
Jingzhan Huang ◽  
Jin Lan ◽  
Kun Zhou ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Western Blot ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Free Survival ◽  
Gene Set ◽  
Oncomine Database ◽  
Kaplan Meier

Abstract Background Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1. Conclusion CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.

scholarly journals SNHG3/miR-148a-3p Axis–mediated High Expression of DNMT1 Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Ninghua Yao ◽  
Wei Jiang ◽  
Jie Sun ◽  
Chen Yang ◽  
Wenjie Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Immune Cell Infiltration ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Immune Infiltration ◽  
Computer Analyses ◽  
Dnmt1 Expression

Abstract Background Epigenetic reprogramming plays an important role in the occurrence, development, and prognosis of hepatocellular carcinoma (HCC). DNA methylation is a key epigenetic regulatory mechanism, and DNA methyltransferase 1 (DNMT1) is the major enzyme responsible for maintenance methylation. Nevertheless, the role and mechanism of DNMT1 in HCC remains poorly defined. Methods In the current study, we conducted pan-cancer analysis for DNMT1’s expression and prognosis using The Cancer Genome Atlas (TCGA) data set. We conducted gene Set Enrichment Analysis (GSEA) between high-and-low DNMT1 expression groups to identify DNMT1-related functional significance. We also investigated the relationship between DNMT1 expression and tumor immune microenvironment, including immune cell infiltration and the expression of immune checkpoints. Through a combination series of computer analyses (including expression analyses, correlation analyses, and survival analyses), the noncoding RNAs (ncRNAs) that contribute to the overexpression of DNMT1 were ultimately identified. Results We found that DNMT1 was upregulated in 16 types of human carcinoma including HCC, and DNMT1 might be a biomarker predicting unfavorable prognosis in HCC patients. DNMT1 mRNA expression was statistically associated with age, histological grade, and the level of serum AFP. Moreover, DNMT1 level was significantly and positively linked to tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Meanwhile, Gene Set Enrichment Analysis (GSEA) revealed that high-DNMT1 expression was associated with epithelial mesenchymal transition (EMT), E2F target, G2M checkpoint, and inflammatory response. Finally, through a combination series of computer analyses the SNHG3/hsa-miR-148a-3p/DNMT1 axis was confirmed as the potential regulatory pathway in HCC. Conclusion SNHG3/miR-148a-3p axis upregulation of DNMT1 may be related to poor outcome, tumor immune infiltration, and regulated malignant properties in HCC.

scholarly journals Elevated TUBA1A Might Indicate the Clinical Outcomes of Patients with Gastric Cancer, Being Associated with the Infiltration of Macrophages in the Tumor Immune Microenvironment

2020 ◽  
Vol 29 (4) ◽  
pp. 509-522
Author(s):  
Dazhi Wang ◽  
Zheng Jiao ◽  
Yinghui Ji ◽  
Shuyu Zhang
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Single Cells ◽  
Enrichment Analysis ◽  
Clinicopathological Features ◽  
Gene Set Enrichment Analysis ◽  
Regulation Mechanism ◽  
Gene Set Enrichment ◽  
Gene Set

Background and Aims: TUBA1A belongs to the tubulin superfamily, and its role in gastric cancer (GC) remains unclear. This study assessed the expression and effect of TUBA1A in GC, as well as its association with survival and clinicopathological features. Gene set enrichment analysis (GSEA) results revealed that high TUBA1A expression was associated with multiple pathways, including those that contributed to the infiltration of macrophages in the tumor microenvironment. Since increased infiltration of macrophages can lead to oxaliplatin resistance, we analyzed the association between TUBA1A, the infiltration of macrophages to the tumor microenvironment, and the inhibitory concentration 50% (IC50) of oxaliplatin. In addition, we analyzed the possible epigenetic regulation mechanism. Methods: A total of 1,881 samples, including 1,618 patients with GC and 263 normal samples, were examined. The associations between clinicopathological features and TUBA1A were assessed by chi-square test, survival was assessed by Kaplan-Meier analysis, and gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms. The associations between TUBA1A and immune infiltration of M0-, M1-, and M2- polarized macrophages were examined by applying deconvolution’s quantification and Pearson’s correlation analysis. The association of TUBA1A with the IC50 of oxaliplatin was analyzed by Pearson correlation test. The mechanisms of TUBA1A dysregulation were studied by analyzing methylation data. A single-cell TUBA1A mRNA expression map of the stomach was drawn from the analysis of stomach single-cell RNA sequencing data that included more than 13,000 single cells of 17 stomach cell types. Results: TUBA1A expression was elevated in GC (p<0.01) and indicated poorer overall survival (p<0.001), first progression survival (p<0.001), and post-progression survival (p<0.01). High TUBA1A expression was significantly correlated with more aggressive clinicopathological features of GC patients (p<0.001). Elevated TUBA1A contributes to the infiltration of macrophages to the tumor microenvironment (p<0.001) and increased the IC50 of oxaliplatin in vitro (p<0.05), while hypomethylation was shown to contribute to the upregulation of TUBA1A (p<0.05). Conclusions: TUBA1A might be a potential prognostic marker and therapeutic target in GC. TUBA1A is significantly associated with the infiltration of M2-polarized macrophages in GC, and the IC50 of oxaliplatin. Hypomethylation contributes to the upregulation of TUBA1A in GC.

scholarly journals Elevated GAS2L3 Expression Correlates With Poor Prognosis in Patients With Glioma: A Study Based on Bioinformatics and Immunohistochemical Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Zhou ◽  
Limin Zhang ◽  
Sirong Song ◽  
Lixia Xu ◽  
Yan Yan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Immunohistochemical Analysis ◽  
Gene Set Enrichment Analysis ◽  
Immune Checkpoints ◽  
Gene Set Enrichment ◽  
Bioinformatics Analyses ◽  
Gene Set

BackgroundGrowth arrest–specific 2 like 3 (GAS2L3) is a cytoskeleton-associated protein that interacts with actin filaments and tubulin. Abnormal GAS2L3 expression has been reported to be associated with carcinogenesis. However, the biological role of GAS2L3 in glioma remains to be determined.MethodsThe transcriptome level of GAS2L3 and its relationship with clinicopathological characteristics were analyzed among multiple public databases and clinical specimens. Bioinformatics analyses were conducted to explore biological functions and prognostic value of GAS2L3 in glioma.ResultsGAS2L3 was substantially expressed in glioma, and high GAS2L3 expression correlated with shorter overall survival time and poor clinical variables. Gene set enrichment analysis (GSEA), single-sample gene-set enrichment analysis, and CIBERSORT algorithm analyses showed that GAS2L3 expression was closely linked to immune-related pathways, inflammatory activities, and immune cell infiltration. Moreover, GAS2L3 was synergistic with T cell–inflamed gene signature, immune checkpoints, T-cell receptor diversities, and neoantigen numbers.ConclusionThis study suggests that GAS2L3 is a prognostic biomarker for glioma, providing a reference for further study of the potential role of GAS2L3 in the immunomodulation of glioma.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

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