scholarly journals Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanghui Zhao ◽  
Junhua An ◽  
Qian Pu ◽  
Wenwen Geng ◽  
Haiyun Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients ◽  
Gene Signatures ◽  
Immune Phenotypes ◽  
Processing Stability

The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m6A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.

Gene Signatures And Cancer-Immune Phenotypes Based On m6A Regulators In Breast Cancer

2021 ◽  
Author(s):  
Guanghui Zhao ◽  
Junhua An ◽  
Qian Pu ◽  
Wenwen Geng ◽  
Haiyun Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Related Gene ◽  
Immune Microenvironment ◽  
Gene Signatures ◽  
Immune Phenotypes ◽  
Processing Stability

Abstract Background: The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood.Methods: We comprehensively evaluated the genetic variations and transcript expressions of 15 m6A regulators, and clinicopathological features in 1,079 breast cancer samples from The Cancer Genome Atlas (TCGA) database. The mRNA and protein levels of several m6A regulators were validated by RT-qPCR, western blot and immunohistochemistry staining in clinical samples from 39 patients with breast cancer. The prognostic values of m6A regulators were systematically evaluated in different database. We correlated the m6A modification patterns of breast cancer with the immune microenvironment and cancer-immune phenotypes. The m6A regulators-related gene signatures were also analyzed to predict the survival of patients.Results: Some m6A regulators’ CNV events might be potential biomarkers for patient’s stage and prognosis in breast cancer. Major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal samples among different molecular subtypes of breast cancer, and especially high expression of m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A regulators’ pattern showed distinct overall survival, immune activation status and immune cell infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer.Conclusions: The m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Comprehensive evaluation of tumor m6A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.

PD-1+ immune cell infiltration inversely correlates with survival of operable breast cancer patients

2014 ◽  
Vol 63 (4) ◽  
pp. 395-406 ◽  
Author(s):  
Shenyou Sun ◽  
Xiaochun Fei ◽  
Yan Mao ◽  
Xiumin Wang ◽  
David H. Garfield ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cell ◽  
Operable Breast Cancer ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients

scholarly journals Systematic Identification of the Cancer Pathways and Molecules Related With Breast Cancer Immunogenicity

2021 ◽  
Author(s):  
Xiaoli Wang ◽  
Silu Xu ◽  
Lingli Huang ◽  
Lei Wang ◽  
Nan Wu
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Immune Cell ◽  
Positive Association ◽  
Cell Infiltration ◽  
Pathway Enrichment Analysis ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients ◽  
Cancer Pathways ◽  
Molecular Features

Abstract To identify molecular features related to immunogenic activity in breast cancer (BC) and provide new targets and directions for BC immunotherapy. We first used ESTIMATE to evaluate the degree of immune cell infiltration of the BC patients in TCGA and METABRIC, and explore the relationship between the degree of immune cell infiltration and prognosis of breast cancer patients. Then, we identified the cancer pathways, proteins, miRNAs related to BC immunogenicity, and predicted miRNAs target genes and identified the pathways related to target genes with KEGG pathway enrichment analysis. We also explored the correlation between PD-L1 expression level and cancer pathways and found that PD-L1 expression showed a positive association with cancer pathways. In this article we have successfully identified several cancer pathways, proteins, miRNAs and their target genes, which could be as promising new target for BC immunotherapy. And PD-L1 blockade therapy may be more effective in BC patients with the activation of some cancer pathways.

scholarly journals Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinguo Zhang ◽  
Benjie Shan ◽  
Lin Lin ◽  
Jie Dong ◽  
Qingqing Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Immune Cell ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Consensus Clustering ◽  
Prognostic Signature ◽  
Non Coding Rnas

Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.

scholarly journals ITGA3 Is Associated With Immune Cell Infiltration and Serves as a Favorable Prognostic Biomarker for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yue Li ◽  
Fan Li ◽  
Xiaoyu Bai ◽  
Yanlei Li ◽  
Chunsheng Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
Immune Cell ◽  
Genomic Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Diagnostic Value ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients

BackgroundITGA3 is a member of the integrin family, a cell surface adhesion molecule that can interact with extracellular matrix (ECM) proteins. The purpose of this study was to explore the significance of ITGA3 expression in the prognosis and clinical diagnosis of breast cancer patients.MethodsOncomine, the Human Protein Atlas (HPA) and UALCAN were used to analyze the expression of ITGA3 in various cancers. PrognoScan, GEPIA, Kaplan–Meier plotter and Easysurv were utilized to analyze the prognosis of ITGA3 in certain cancers. Based on TCGA data, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of ITGA3 expression. cBio-Portal and MethSurv were used to evaluate the genomic mechanism. LinkedOmics, NetworkAnalyst and Metascape were used to build the signaling network. TIMER is a web server for comprehensive analysis of tumor infiltrating immune cells and tumor infiltrating lymphocytes (TILs).ResultsThe expression of ITGA3 in normal breast tissues was greater than that in breast cancer tissues at both the mRNA and protein levels. High expression of ITGA3 was associated with better prognosis of breast cancer patients. ROC analysis indicated that ITGA3 had significant diagnostic value. Genomic analysis revealed that promoter methylation of ITGA3 leads to transcriptional silencing, which may be one of the mechanisms underlying ITGA3 downregulation in BRCA. Immune infiltration analysis showed that ITGA3 may be involved in the recruitment of immune cells.ConclusionsThis study identified ITGA3 as a novel biomarker to estimate the diagnosis and prognosis of breast cancer. In addition, ITGA3 is involved in ECM regulation and immune cell infiltration.

scholarly journals Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
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.

scholarly journals Correlation Between 18F-FDG Uptake and Immune Cell Infiltration in Metastatic Brain Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Young-Sil An ◽  
Se-Hyuk Kim ◽  
Tae Hoon Roh ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Standardized Uptake Value ◽  
Brain Lesions ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Ki 67 ◽  
Glucose Transporter 1 ◽  
Fdg Uptake

BackgroundThe purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.MethodsThis retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.ResultsThe degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.ConclusionsIn metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.

Atlas of immune cell infiltration in breast cancer—high M2 macrophage and low native B cellproportions are associated with poor survival

2021 ◽  
Vol 0 ◽  
pp. 0-0
Author(s):  
Lei Fan ◽  
Lin-Xiaoxi Ma ◽  
Peng Zhou ◽  
Zhi-Ming Shao
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Poor Survival
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