scholarly journals Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Jia Lv ◽  
Yongze Zhu ◽  
Alin Ji ◽  
Qi Zhang ◽  
Guodong Liao
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Clinical Significance ◽  
Immune Cells ◽  
Prognostic Value ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Ras Signaling ◽  
High Morbidity

Abstract Background: Bladder cancer is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Tumor mutational burden (TMB) is an emerging biomarker in cancer characterized by microsatellite instability. TMB has been described as a powerful predictor of tumor behavior and response to immunotherapy. Methods: A total of 443 bladder cancer samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for mutation types, TMB values, and prognostic value of TMB. Differentially expressed genes (DEGs) were identified from the TMB groupings. Functional analysis was performed to assess the prognostic value of the first 30 core genes. CIBERSORT algorithm was used to determine the correlation between the immune cells and TMB subtypes. Results: Single nucleotide polymorphism (SNP) and C>T were reported as the most common missense mutations and we also identified a high rate of mutations in TP53, TTN, KMT2D. Bladder cancer patients with high TMB showed a better prognosis. Enrichment analysis of the DEGs revealed that they were involved in the regulation of the P13K-Akt signaling pathway, cytokine–cytokine receptor interaction, and Ras signaling pathway. The high expression of hub genes ADRA2A, CXCL12, S1PR1, ADAMTS9, F13A1, and SPON1 was correlated with poor overall survival. Besides, significant differences in the composition of the immune cells of T cells CD8, T cells CD4 memory activated, NK cells resting and Mast cells resting were observed. Conclusions: The present study provides a comprehensive and systematic analysis of the prediction of TMB in bladder cancer and its clinical significance. Also, the study provides additional prognostic information and opportunities for immunotherapy in bladder cancer.

scholarly journals Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8348
Author(s):  
Mei Chen ◽  
Shufang Zhang ◽  
Xiaohong Wen ◽  
Hui Cao ◽  
Yuanhui Gao
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Multivariate Analyses ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Normal Tissues

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Kai Gan ◽  
Yue Gao ◽  
KuangZheng Liu ◽  
Bin Xu ◽  
Ming Chen
Keyword(s):  
Bladder Cancer ◽  
Clinical Significance ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Her2 Expression ◽  
Large Tumor ◽  
Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

scholarly journals A gene expression-based study on immune cell subtypes and glioma prognosis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiu-Yue Zhong ◽  
Er-Xi Fan ◽  
Guang-Yong Feng ◽  
Qi-Ying Chen ◽  
Xiao-Xia Gou ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Data Analysis ◽  
Nk Cells ◽  
Immune Cells ◽  
Prognostic Value ◽  
Immune Cell ◽  
High Morbidity ◽  
Gamma Delta T Cells ◽  
Gamma Delta

Abstract Object Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma. Methods We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample. Results In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8+ T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis. Conclusion We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.

scholarly journals Screening and Identification of an Immune-Associated lncRNA Prognostic Signature in Ovarian Carcinoma: Evidence from Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yan Li ◽  
Fan-fan Huo ◽  
Ying-ying Wen ◽  
Miao Jiang
Keyword(s):  
Ovarian Carcinoma ◽  
Risk Score ◽  
Immune Cells ◽  
Prognostic Value ◽  
Antigen Processing ◽  
Multivariate Analyses ◽  
Wnt Signaling Pathway ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Backgrounds. The dysregulated long noncoding RNAs (lncRNAs) have been described to be crucial regulators in the progression of ovarian carcinoma. The infiltration status of immune cells is also related to the clinical outcomes in ovarian carcinoma. The present research is aimed at constructing an immune-associated lncRNA signature with potential prognostic value for ovarian carcinoma patients. Methods. We obtained 379 ovarian carcinoma cases with available clinical data and transcriptome data from The Cancer Genome Atlas database to evaluate the infiltration status of immune cells, thereby generating high and low immune cell infiltration groups. According to the expression of the immune-associated lncRNA signature, the risk score of each case was calculated. The high- and low-risk groups were classified using the median risk score as threshold. Results. A total of 169 immune-associated lncRNAs that differentially expressed in ovarian carcinoma were included. According to the Lasso regression analysis and Cox univariate and multivariate analyses, 5 immune-associated lncRNAs, including AC134312.1, AL133467.1, CHRM3-AS2, LINC01722, and LINC02207, were identified as a predictive signature with significant prognostic value in ovarian carcinoma. The following Kaplan-Meier analysis, ROC analysis, and Cox univariate and multivariate analyses further suggested that the predicted signature may be an independent prognosticator for patients with ovarian carcinoma. The following gene set enrichment analysis showed that this 5 immune-associated lncRNAs signature was significantly related to the hedgehog pathway, basal cell carcinoma, Wnt signaling pathway, cytokine receptor interaction, antigen processing and presentation, and T cell receptor pathway. Conclusion: This study suggested a predictive model with 5 immune-associated lncRNAs that has an independent prognostic value for ovarian carcinoma patients.

scholarly journals Biglycan Overexpression Predicts Poor Prognosis of Gastric Cancer

2021 ◽  
Author(s):  
Xin-zhou Huang ◽  
Hui Chen ◽  
Wen-ming Song ◽  
Ying-ying Wang ◽  
Meiyuan Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Receptor Interaction ◽  
Significant Implication ◽  
Mrna Levels

Abstract Background: Biglycan (BGN) encodes an extracellular matrix (ECM) proteoglycan. However, the potential diagnostic and prognostic value of BGN in gastric cancer (GC) have not yet been reported. In this analysis, BGN expression in GC was evaluated across the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Oncomine databases, and verified using immunohistochemistry (IHC). The relationship between BGN expression and clinicopathological parameters was assessed by chi-square test and logistic regression. We analyzed the prognostic value of BGN. Then, Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in high BGN expression datasets in GC. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in GC tissues, and the correlation between BGN and infiltrating immune cells was analyzed.Results: The results showed that the mRNA levels of BGN were significantly up-regulated in GC compared with normal tissues (all P <0.001). The Kaplan-Meier plotter online database suggested that patients with high BGN expression had a poor prognosis (P=1.3e-10). In addition, using gene sets analysis, we found that pathways of bladder cancer, Wnt-signaling, TGF-beta signaling, and ECM-receptor interaction were differentially activated in high-expression BGN tissues. Furthermore, CIBERSORT analysis for the proportion of TICs revealed that macrophages M2 was positively correlated with BGN expression. Conclusions: In conclusion, BGN can be used as potential diagnostic markers of GC, and immune cell infiltration plays an important role in the occurrence and progression of GC. The finding may have significant implication for the diagnosis, prognosis and treatment of GC.

scholarly journals The Construction and Analysis of Tumor-Infiltrating Immune Cells and ceRNA Networks in Bladder Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Aimin Jiang ◽  
Na Liu ◽  
Shuheng Bai ◽  
Jingjing Wang ◽  
Huan Gao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Pearson Correlation ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Cerna Network ◽  
Follicular Helper ◽  
Pearson Correlation Test

BackgroundBladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak.ObjectivesThis study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients.MethodsThe expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells.ResultsA total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells.ConclusionOur results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2, and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA.

scholarly journals EPDR1 is related to stages and metastasize in bladder cancer and can be used as a prognostic biomarker

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yue Yang ◽  
Hanchao Zhang ◽  
Zhengdao Liu ◽  
Faliang Zhao ◽  
Guobiao Liang
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Prognostic Biomarker ◽  
Transmembrane Protein ◽  
Tumor Stage ◽  
Receptor Interaction ◽  
Advanced Tumor Stage ◽  
Normal Bladder ◽  
Advanced Tumor ◽  
Significant Difference

AbstractBackgroundBladder cancer (BLCA) is a malignant urothelial carcinoma and has a high mortality rate. EPDR1 (ependymin related 1) is a type II transmembrane protein and related to calcium-dependent cell adhesion.MethodsWe explored the potential oncogenic roles of EPDR1 in BLCA basing on the multiple public datasets.ResultsWe found that EPDR1 expression had a significant difference in BLCA and adjacent normal bladder tissues, and the level of EPDR1was up-regulated with advanced tumor stage and metastasis in BLCA. Meanwhile, the high expression group of EPDR1 had a shorter OS compared to the low or medium expression-group. Furthermore, EPDR1 expression was associated with tumor-infiltrating immune cells (TIICs), including NK cells, CD8 + T cells, CD4 + T cells, Macrophages cells, and so on. Moreover, EPDR1 also involved in several signaling pathways as well as PI3K/AKT pathway, Cytokine receptor interaction, and apoptosis.ConclusionEPDR1 can be used as a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.

scholarly journals The Analysis of PTPN6 for Bladder Cancer: An Exploratory Study Based on TCGA

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chengquan Shen ◽  
Jing Liu ◽  
Jirong Wang ◽  
Xiaokun Yang ◽  
Haitao Niu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Survival Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Tyrosine Phosphatase ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Pathologic Features ◽  
The Relationship

PTPN6 (protein tyrosine phosphatase nonreceptor type 6), a tyrosine phosphatase, is known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Previous studies have demonstrated that PTPN6 expression is relatively elevated in several malignancies. However, the role of PTPN6 in bladder cancer (BC) remains unclear. The purpose of this study was to explore the prognostic value of PTPN6 in BC. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify the expression level of PTPN6 in BC. The relationship between clinical pathologic features and PTPN6 were analyzed with the Wilcoxon signed-rank test. The prognostic and predictive value of PTPN6 was evaluated by survival analysis and nomogram. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential molecular mechanisms of PTPN6 in BC. Finally, Tumor Immune Estimation Resource (TIMER) was applied to investigate the relationship between PTPN6 and immune cell infiltration in the tumor microenvironment. Results indicated that PTPN6 was overexpressed in BC tissues compared with normal bladder tissues and was significantly correlated with grade, stage, T, and N. Survival analysis showed that low expression of PTPN6 was significantly related to the poor overall survival (OS) in BC patients. Coexpression analysis showed that PTPN6 and TNFRSF14 (Tumor necrosis factor receptor superfamily member 14) have a close correlation in BC. GSEA showed that multiple cancer-associated signaling pathways are differentially enriched in the PTPN6 high expression phenotype. Moreover, the expression level of PTPN6 was positively associated with the infiltration of B cells, CD4+T cells, dendritic cells, and neutrophils and negatively associated with CD8+ T cells and macrophages in BC. In conclusion, we identified that PTPN6 may be a novel prognostic biomarker in BC based on the TCGA database. Further clinical trials are needed to confirm our observations and mechanisms underlying the prognostic value of PTPN6 in BC also deserve further experimental exploration.

Prognostic value of peripheral naive CD8+ T cells in oligometastatic non-small-cell lung cancer

2021 ◽  
Author(s):  
Xin Zhao ◽  
Yan Zhang ◽  
Zhenlin Gao ◽  
Yaguang Han
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

scholarly journals CILP Inhibits Brain Metastasis by Meditating Mast Cells via the MAPK Signaling Pathway in Breast Cancer

2021 ◽  
Author(s):  
Xiaolin Sun ◽  
Xingguo Zhou ◽  
Alei Feng ◽  
Gongwen Xu ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mast Cells ◽  
Correlation Analysis ◽  
Brain Metastases ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Cell Activity ◽  
Mapk Signaling ◽  
High Morbidity ◽  
Spearman’S Correlation

Abstract Background: Approximately 15–30% of patients with breast cancer (BRCA) eventually develop brain metastases (BMs) with high morbidity and mortality. Herein, we aimed to identify genes specific to breast cancer brain metastases (BCBM) from an immune infiltration perspective.Methods: GSE100534 and GSE125989 were obtained from the NCBI Gene Expression Omnibus (GEO), then performed normalization using Rstudio and perl 5. We constructed a Weighted Gene Co-Expression Network Analysis (WGCNA) and obtained differentially expressed genes (DEGs) in BMs sample compared with primary BRCA tissue. Then we performed GO and KEGG pathway analysis. The LinkedOmics and UALCAN analysis showed the expression of gene in BRCA. The Kaplan-Meier plotter database was used to evaluate the prognosis. The composition of significant tumor-infiltrating immune cells was assessed using the CIBERSORT algorithm. Spearman’s correlation analysis revealed the correlation between CILP gene and immune cells in TCGA cohort and Timer database. Using GSEA analysis, we conducted to identify the potential pathways in BCBM.Results: The cartilage intermediate layer protein (CILP) was a late event in BRCA (stage III to IV) with poor prognosis (P< 0.05). LinkedOmics showed that the mRNA expression of CILP was down-regulated in advanced cancer (P< 0.05). Besides, UALCAN analysis showed that CILP expression was downregulated in HER2-positive and triple-negative breast cancer which were more prone to BMs (P< 0.05). CILP was the hub gene which was significantly associated with BCBM identified by WGCNA (R2=−0.6, P=3e-06). We found that the resting infiltration of mast cells in the BCBM group was significantly lower than that in the primary BRCA group (P= 0.01). In addition, Spearman’s correlation analysis revealed that the expression of CILP positively correlated with that of mast cells (P< 0.05). Finally, the FCERI-mediated MAPK activation (NES=2.1847, P=0, FDR=0.0031), which could regulate mast cell activity, were enriched in BCBM.Conclusions: CILP can influence the progression of BRCA favored for BMs through meditating mast cells via the MAPK signaling pathway.

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