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

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.

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Prognostic Value of BTNL9 Combined with Genes of Proteasome and Ubiquitin System in Pancreatic Cancer

10.21203/rs.3.rs-955285/v1 ◽

2021 ◽

Author(s):

Ke Xu ◽

Qingfan Mo ◽

Bo Liu ◽

Rongfei Huang ◽

Wei Zhou ◽

...

Keyword(s):

Pancreatic Cancer ◽

Prognostic Factors ◽

Prognostic Value ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Immune Checkpoints ◽

Prognostic Prediction ◽

The Relationship

Abstract Background: An accurate prognostic prediction can improve the individualized management of patients with pancreatic cancer (PC), and the exploration of biomarkers with prognostic value for clinical practice is the prerequisite of the work. Butyrophilin-Like 9 (BTNL9) has recently been found to function as a tumor suppressor gene in a variety of malignancies and has the potency to serve as a prognostic biomarker. Our aim was to explore the relationship between BTNL9 expression and the prognosis of PC, and to unearth its upstream and downstream molecular mechanisms. Methods: The RNA expression of BTNL9 was analyzed in 5 datasets from Gene Expression Omnibus (GEO) database. The protein expression of BTNL9 was detected by immunohistochemistry in a cohort including 42 PC patients. The relationship between BTNL9 expression and prognosis was analyzed by survival and prognostic factors analysis. Online database and Gene Set Enrichment Analysis (GSEA) were used to explore the upstream and downstream molecular mechanisms of BTNL9. Correlation analysis and CIBERSORT were applied to investigate the relationship between BTNL9 and tumor immunology.Results: In multiple datasets and our cohort, BTNL9 expression was decreased in PC tissues. Patients with high expression of BTNL9 had a better prognosis. BTNL9, age and N stage were identified as the independent prognostic factors of PC. BTNL9 was predicted to be down-regulated by hsa-miR-1910-5p, and it may be involved in the proteasome and PC signaling pathway. Interestingly, genes of proteasome (PSMD2, PSMD7 and PMSD14) and deubiquitin system (USP20, USP27X and USP30) combined BTNL9 could improve the prognostic prediction of PC. In addition, the expression of BTNL9 correlates with the expression of immune checkpoints and influences the infiltration of tumor immune cells. Conclusions: BTNL9 can serve as a prognostic marker of PC, and high expression of BTNL9 was generally associated with better prognosis. Combined the expression of BTNL9 and the expression of PSMD2, PSMD7, PMSD14, USP20, USP27X and USP30 can more accurately analyze the prognosis of patients with PC.

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Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

10.21203/rs.3.rs-70360/v1 ◽

2020 ◽

Author(s):

Ran-ran Zhou ◽

Hu Tian ◽

Cheng Yang ◽

Fan Peng ◽

Hao-yu Yuan ◽

...

Keyword(s):

Immune Response ◽

Bladder Cancer ◽

Risk Score ◽

Prognostic Value ◽

Molecular Mechanisms ◽

Cox Regression ◽

External Validation ◽

Gene Set Enrichment Analysis ◽

Prognostic Signature ◽

Cerna Network

Abstract Background: Immunotherapy has been proved to be effective for bladder cancer (BLCA). However, the molecular network involved in BLCA tumor immune response remains unclear. This study aims to construct an immune-related ceRNA network and to identify the prognostic value. Methods: Based on The Cancer Genome Atlas (TCGA), we used single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA) to determine immune-related mRNA, lncRNA and miRNA. Then least absolute shrinkage, and selection operator (LASSO) and Cox regression were performed to identify the mRNAs with high prognostic value, and accordingly, the risk score was calculated. Internal and external validation were performed both in TCGA and GSE13507 with Kaplan-Meier (KM) survival and Receiver Operating Characteristic (ROC) curve analysis. Using the immune-related mRNA, lncRNA and miRNA, a ceRNA network was established via MiRcode, starBase, miRDB, miRTarBase and TargetScan. Besides, we also explore the relationship between the risk score and immune cell infiltration via CIBERSORT algorithm. Results: 5 mRNAs (PCGF3, FASN, DPYSL2, TGFBI and NTF3) were ultimately identified, and KM survival analysis displayed the 5-mRNA risk signature could predict the prognosis of BLCA with high efficacy both in TCGA (p = 1.006e-13) and GSE13507 (p = 7.759e-04). Using miRNA targeting molecular prediction database, an immune-related ceRNA network, including 5 mRNAs, 24 miRNAs and 86 lncRNAs, was constructed. Memory B cells, activated dendritic cells, and regulatory T cells infiltration into tumors were negatively correlated with risk score, while the infiltration levels of macrophages M0, M1 and M2 were positively correlated with risk score. Conclusion: This study helped to better understand the molecular mechanisms of tumor immune response from the view of ceRNA hypothesis, and provided a novel prognostic signature for bladder cancer.

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In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820986826 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098682

Author(s):

Zhipeng Zhu ◽

Jiuhua Xu ◽

Xiaofang Wu ◽

Sihao Lin ◽

Lulu Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Subgroup Analysis ◽

Prognostic Value ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Clinicopathological Parameters ◽

Free Survival ◽

Cox Regression Analysis ◽

The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

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Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽

10.7717/peerj.8348 ◽

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.

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Bladder Cancer in the Genomic Era

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2018-0329-ra ◽

2019 ◽

Vol 143 (6) ◽

pp. 695-704 ◽

Cited By ~ 6

Author(s):

Charles C. Guo ◽

Bogdan Czerniak

Keyword(s):

Bladder Cancer ◽

Molecular Mechanisms ◽

Complex Disease ◽

Human Cancer ◽

Wide Spectrum ◽

Clinicopathologic Features ◽

Pathologic Features ◽

Genomic Characterization

Context.— Bladder cancer is a heterogeneous disease that exhibits a wide spectrum of clinical and pathologic features. The classification of bladder cancer has been traditionally based on morphologic assessment with the aid of immunohistochemistry. However, recent genomic studies have revealed that distinct alterations of DNA and RNA in bladder cancer may underlie its diverse clinicopathologic features, leading to a novel molecular classification of this common human cancer. Objective.— To update recent developments in genomic characterization of bladder cancer, which may shed insights on the molecular mechanisms underlying the origin of bladder cancer, dual-track oncogenic pathways, intrinsic molecular subtyping, and development of histologic variants. Data Sources.— Peer-reviewed literature retrieved from PubMed search and authors' own research. Conclusions.— Bladder cancer is likely to arise from different uroprogenitor cells through papillary/luminal and nonpapillary/basal tracks. The intrinsic molecular subtypes of bladder cancer referred to as luminal and basal exhibit distinct expression signatures, clinicopathologic features, and sensitivities to standard chemotherapy. Genomic characterization of bladder cancer provides new insights to understanding the biological nature of this complex disease, which may lead to more effective treatment.

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Increased Expression of LYNX1 in Ovarian Serous Cystadenocarcinoma Predicts Poor Prognosis

BioMed Research International ◽

10.1155/2020/1392674 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Hui Liu ◽

Ao Wang ◽

Yushan Ma

Keyword(s):

Ovarian Cancer ◽

Univariate Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Gene Set ◽

Serous Cystadenocarcinoma ◽

Kaplan Meier ◽

Pathologic Features ◽

The Relationship

Few studies have reported the function of LYNX1 in ovarian cancer. We retrieved LYNX1 gene expression data and clinical information of 376 patients with ovarian cancer from The Cancer Genome Atlas (TCGA) project website. Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical pathologic features and LYNX1 expression. The Kaplan–Meier method was used to draw survival curves of patients, and Cox regression was used to calculate the relationship between LYNX1 expression and survival rate or the clinicopathological characteristics of the patients. Gene set enrichment analysis (GSEA) was performed, and the correlation between LYNX1 expression and cancer immune infiltrates was investigated via single sample gene set enrichment analysis (ssGSEA). High LYNX1 expression in ovarian serous cystadenocarcinoma (OVs) was associated with tumor residual disease (RD). In Kaplan–Meier survival analysis, patients with OVs who also displayed high LYNX1 expression had decreased overall survival (OS) and disease-specific survival (DSS) than those with low LYNX1 expression. Univariate analysis also supported that patients with high LYNX1 expression had lower OS than those with low LYNX1 expression. LYNX1 expression has the potential to be a prognostic molecular marker of poor survival in OVs.

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Identification of an IRGP Signature to Predict Prognosis and Immunotherapeutic Efficiency in Bladder Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.607090 ◽

2021 ◽

Vol 8 ◽

Author(s):

Liang-Hao Zhang ◽

Long-Qing Li ◽

Yong-Hao Zhan ◽

Zhao-Wei Zhu ◽

Xue-Pei Zhang

Keyword(s):

Bladder Cancer ◽

Stromal Cells ◽

Molecular Mechanisms ◽

Proportional Hazards ◽

Enrichment Analysis ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Consensus Clustering ◽

Validation Set

BackgroundIdentify immune-related gene pairs (IRGPs) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients.Materials and MethodsOne RNA-seq dataset (The Cancer Genome Atlas Program) and two microarray datasets (GSE13507 and GSE31684) were included in this study. We defined these cohorts as training set to construct IRGPs and one immunotherapy microarray dataset as validation set. Identifying BLCA subclasses based on IRGPs by consensus clustering. The Lasso penalized Cox proportional hazards regression model was used to construct prognostic signature and potential molecular mechanisms were analyzed.ResultsThis signature can accurately predict the overall survival of BLCA patients and was verified in the immunotherapy validation set. IRGP-signatures can be used as independent prognostic risk factor in various clinical subgroups. Use the CIBERSORT algorithm to assess the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. According to the results of GSVA, GSEA, and CIBERSORT algorithm, we found that IRGP is strikingly positive correlated with tumor microenvironment (TME) stromal cells infiltration, indicating that the poor prognosis and immunotherapy might be caused partly by enrichment of stromal cells. Finally, the results from the TIDE analysis revealed that IRGP could efficiently predict the response of immunotherapy in BLCA.ConclusionThe novel IRGP signature has a significant prognostic value for BLCA patients might facilitate personalized for immunotherapy.

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SPP1 Might Be a Novel Prognostic Biomarker for Patients With Malignancy: a Meta-analysis and Sequential Verification Based on Bioinformatic Analysis

10.21203/rs.3.rs-132455/v1 ◽

2020 ◽

Author(s):

Hao-ran Zheng ◽

Ai-Min Jiang ◽

Na Liu ◽

Qian-Qian Ding ◽

Fu-Mei Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Lipid Metabolism ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Cochrane Library ◽

The Relationship

Abstract Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.

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SPP1 Might Be A Novel Prognostic Biomarker For Patients With Malignancy: A Meta-Analysis And Sequential Verification Based on Bioinformatic Analysis

10.21203/rs.3.rs-120265/v1 ◽

2020 ◽

Author(s):

Haoran Zheng ◽

Ai-Min Jiang ◽

Na Liu ◽

Qian-Qian Ding ◽

Fu-Mei Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Lipid Metabolism ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Cochrane Library ◽

The Relationship

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The relationship of the tertiary lymphoid structures with the tumor-infiltrating lymphocytes and its prognostic value in gastric cancer

Archives of Medical Science ◽

10.5114/aoms/140622 ◽

2021 ◽

Author(s):

Nana Zhang ◽

Guanjun Zhang ◽

Depu Wang ◽

Hao Liu ◽

Yuchi Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Prognostic Value ◽

Tumor Infiltrating Lymphocytes ◽

High Endothelial Venules ◽

Tumor Center ◽

Tertiary Lymphoid Structures ◽

Lymphoid Structures ◽

Infiltrating Lymphocytes ◽

The Relationship

IntroductionTo explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC).Material and methodsThe TLSs and four subtypes of TILs were assessed by immunohistochemistry (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as a valid TLSs.The number of labeled TILs were observed in 5 fields of the most positive cells in tumor center, invasive edge and within the TLSs, respectively, at a field of vision×40.ResultsThe TLSs distributed significantly higher in the tumor invasive edge than the tumor center (P <0.001). Similarly, the infiltrating density of CD8+T cells and GrB+T cells were highly distributed in the tumor infiltrating edge than the tumor center. While the total number of TILs and the FOXP3+T cells were on the contrary. There was a positive correlation between the density of TLSs and TILs either in the location or the immune phenotype. And a higher frequency of TILs and TLSs often associated with the favorable clinicopathologic parameters. Multivariate analysis revealed that the density of TILs (P= 0.019) and TLSs (P= 0.037) were the independent prognostic predictor for GC patients.ConclusionsThe formation of TLSs predicts an advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients and as a marker of efficient immunotherapies.

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