scholarly journals The ncRNA-Mediated Overexpression of Ferroptosis-Related Gene EMC2 Correlates With Poor Prognosis and Tumor Immune Infiltration in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xing Liu ◽  
Pengshuo Yang ◽  
Lu Han ◽  
Qing Zhou ◽  
Qingsong Qu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Invasive Carcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Death Process ◽  
Immune Cell Infiltration ◽  
Related Gene ◽  
Expression Levels ◽  
Immune Infiltration

Ferroptosis is an iron-dependent programmed cell death process. Although ferroptosis inducers hold promising potential in the treatment of breast cancer, the specific role and mechanism of the ferroptosis-related gene EMC2 in breast cancer have not been entirely determined. The potential roles of EMC2 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor Immune Estimation Resource (TIMER), Shiny Methylation Analysis Resource Tool (SMART), starBase, and cBioPortal for cancer genomics (cBioPortal) datasets. The expression difference, mutation, survival, pathological stage, DNA methylation, non-coding RNAs (ncRNAs), and immune cell infiltration related to EMC2 were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the differences in biological processes and functions among different related genes. The expression levels of core prognostic genes were then verified in breast invasive carcinoma samples using immunohistochemistry and breast invasive carcinoma cell lines using real-time polymerase chain reaction. High expression levels of EMC2 were observed in most cancer types. EMC2 expression in breast cancer tissue samples correlated with poor overall survival. EMC2 was mutated and methylated in a variety of tumors and affected survival. The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Our study offers a comprehensive understanding of the oncogenic roles of EMC2 across different tumors. The upregulation of EMC2 expression mediated by ncRNAs is related to poor prognosis and tumor immune infiltration in breast cancer.

scholarly journals Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

scholarly journals Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

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.

scholarly journals CLEC10A is A Prognostic Biomarker and is Correlated with Immune Infiltrates in Breast Cancer

2021 ◽  
Author(s):  
Shasha Tang ◽  
Yi Zhang ◽  
Xiaoyan Lin ◽  
Chunmei Cen ◽  
Liyun Yong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mrna Levels ◽  
Gene Markers ◽  
Normal Tissues ◽  
Potential Biomarker

Abstract Background To investigate the association between CLEC10A and prognosis in breast cancer (BC) patients. Methods We assessed the prognostic value of CLEC10A in BC using data from The Cancer Genome Atlas (TCGA) online database. We examined CLEC10A expression differences in BC and normal tissues via the TIMER and UALCAN databases. Then, we used the Kaplan-Meier plotter database to evaluate the correlation of CLEC10A mRNA levels with clinical outcomes. Subsequently, the TIMER platform and TISIDB website were used to assess the correlation of CLEC10A with the tumor immune cell infiltration level in BC. Results Our results showed that CLEC10A levels were significantly downregulated in BC tissues compared with normal tissues. CLEC10A expression was associated with histologic type, pathologic stage, T stage, Her2 status and a poor prognosis. Additionally, CLEC10A was positively related to the level of different tumor-infiltrating immune cells in BC, and CLEC10A was closely correlated with the gene markers of diverse immune cells. Additionally, low CLEC10A expression predicted a poor prognosis in BC patients grouped based on immune cell infiltration levels. Conclusion CLEC10A may be a potential biomarker and may efficiently predict prognosis in BC patients.

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.

Identification of a Metabolism-Related Risk Signature to Predict the Outcome and Immune Infiltration of Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Yu Liu ◽  
Liyu Wang ◽  
Hengchang Liu ◽  
He Tian ◽  
Tao Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Plasma Cells ◽  
Immune Cell ◽  
Gene Signature ◽  
Metabolic Reprogramming ◽  
Immune Cell Infiltration ◽  
Related Gene ◽  
Prognostic Signature ◽  
Immune Infiltration

Abstract Background: Metabolic reprogramming is associated with tumor heterogeneity and progression. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) might help us to uncover new biomarkers for patient outcomes and targets for therapies.Methods: In this study, metabolism-related genes were screened from mRNA microarray data (GSE53624, GSE53622). Consensus clustering analysis was used to divide tumors into subgroups. Survival analysis and univariate Cox analysis were performed to select prognostic genes. A metabolism-related gene signature was established with multivariate Cox proportional hazards regression (PHR) analysis in the training group (GSE53624). Gene set enrichment analysis (GSEA) and CIBERSORT were used to analyze functional enrichment and immune cell infiltration.The gene signature and immune infiltration were verified in two public databases (GSE53622, TCGA-ESCC) and in two independent cohorts, 95 and 119 ESCC patients, by immunohistochemistry (IHC) analysis. Results: Based on prognosis-related metabolic gene expression, three cluster subgroups (k = 3) were identified with significantly different immune cell infiltration patterns, clinical features and overall survival (OS) times. Then, we developed a multigene (INPP5E, CD38 and POLR3G) prognostic signature that showed better predictive ability and was found to be an independent prognostic risk factor in ESCC database and two public database analyses. This result could also be verified by multicenter IHC experiment and indicated the clinical application potential. In addition, GSEA showed that several tumor-related pathways were associated with the prognostic signature. Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells displayed an obvious correlation with prognostic signature and IHC experiment in 119 cohort also support this result.Conclusions: Our study indicated that the metabolism-related prognostic gene could stratify patients into subgroups and was associated with immune infiltration, clinical features and outcomes. The three-gene prognostic signature from metabolic-related gene displays a good ability to predict OS and the infiltration of immunosuppressive Tregs and plasma cells.

Distinct genomic and immune microenvironment between thymomas and thymic carcinomas.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13529-e13529
Author(s):  
Kaicheng Wang ◽  
Suxia Lin ◽  
Xue Hou ◽  
Yongdong Liu ◽  
Meichen Li ◽  
...  
Keyword(s):  
Immune Cell ◽  
Immune Escape ◽  
Nk Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Immune Microenvironment ◽  
Tissue Samples ◽  
Thymic Epithelial Tumors ◽  
Immune Infiltration ◽  
Thymic Carcinomas

e13529 Background: Thymomas and thymic carcinomas which uniformly known as thymic epithelial tumors (TETs) are rare intrathoracic malignancies and a limited studies have been reported addressing the molecular biology and immune discrepancy. The main purpose of this study was to depict the genomic and transcriptomic landscape of thymomas and thymic carcinomas, as well as elucidate the differentiated immune microenvironment. Methods: Totally 15 thymomas and 7 thymic carcinomas patients were enrolled from January 2014 to July 2018. Treatment-naïve tissue samples were collected, and we also obtained matched peripheral blood mononucleocytes as negative control. DNA and RNA were co-extracted and performed with whole exon and transcriptome sequencing. The immune cell infiltration scores were estimated using ssGSEA algorithm. Results: Exome sequencing revealed that GTF2I mutation occurred in all of type A thymomas but was absent in the aggressive subtypes. The median tumor mutation burden of thymomas was 0.12/Mb, significantly lower than thymic carcinomas (median: 1.02/Mb, p = 0.001). Copy number variation was more common in thymic carcinomas than thymomas (83.3% vs 9.1%, p = 0.005). Top mutational signatures enriched in both thymomas and thymic carcinomas included age and Aristolochic acid exposure, while the APOBEC signature was more common in thymomas than thymic carcinomas (81.8% vs 16.7%, p = 0.03). As a confirmed immune escape event, loss of heterozygosity of human leukocyte antigen was identified in 9.1% of thymomas and 50% of thymic carcinomas. Via unsupervised clustering of immune infiltration, all tissue samples were classified into high- and low-infiltration subgroups. Remarkably, up to 71.4% of samples from thymic carcinomas and only 6.7% of samples from thymomas were defined as low immune cell infiltration. In consideration of specific immune cell types, macrophage ( p = 0.01) and neutrophil ( p = 0.02) were enriched in thymic carcinomas while CD56+ NK cell ( p = 0.005) was enriched in thymomas, indicating the evidential discrepancy about immune cell infiltration between two subtypes of TETs. Conclusions: This study elucidated the molecular and immune microenvironment discrepancy between two subtypes of TETs. From molecular perspective, thymomas and thymic carcinomas are entirely different diseases with different etiology and characterized by distinct immune infiltration, and thus should be managed with disparate therapeutic strategies. Findings in this study may also be useful in future targets development and exploration of immunotherapies in TETs.

Sign in / Sign up

Export Citation Format

Share Document