Immune and Stromal Signature-Based Prognostic Gene of Bladder Cancer

Abstract Background: Immune and stromal cells in the tumor microenvironment have exhibit critical relevance with tumorigenesis and progression. Therefore, our analysis was conducted to explore the potential prognostic factors and the therapeutic targets of bladder cancer (BC) that affiliate to immune and stromal infiltration signature.Methods: Immune and stromal score were calculated for BC patients from TCGA database using ESTIMATE algorithm to predict the level of infiltration. Kaplan-Meier curves were utilized to assess the correlation of immune/stromal infiltration with survival outcomes. Differential expression genes (DEGs) were identified. Enrichment analyses, Kaplan-Meier curves, protein-protein interaction (PPI) network construction were performed to describe and screen the core module genes, whose prognostic value was further validated by an independent GEO dataset. Transcriptional factors (TFs) and ncRNA. correlated with the core module were identified using RAID 2.0 and TRRUST 2.0 database, and drugs potentially regulative for BC were accordingly screened using DrugBank.Results: 393 and 93 BC patients were enrolled from TCGA and GEO respectively. Higher stromal infiltration indicated worse overall survival (P = 0.015), and higher immune infiltration indicated an improvement on overall survival (P = 0.042). 562 DEGs were identified and 123 of them associated with survival outcomes. PPI has identified the core module genes, in which EFNB2 was the only core prognostic gene that was validated by both TCGA (P = 0.042) and GEO dataset (P = 0.036). Four TFs and Five ncRNAs (e.g. HIF1A) were associated with the regulation of the core module genes, and six drugs were screened as potential candidates to regulate BC.Conclusion: Higher immune infiltration in bladder tumor was correlated with improved survival and higher stromal infiltration corelated with worse survival. Furthermore, a higher expression of EFNB2 was tied with poorer prognosis of BC, which was validated by two independent datasets.

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Based on Integrated Bioinformatics Analysis Identification of Biomarkers in Hepatocellular Carcinoma Patients from Different Regions

BioMed Research International ◽

10.1155/2019/1742341 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

Linxin Teng ◽

Kaiyuan Wang ◽

Yu Liu ◽

Yanxia Ma ◽

Weiping Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Biomarkers ◽

Principal Component ◽

Roc Curves ◽

Core Gene ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Protein Protein Interaction ◽

The Core ◽

Kaplan Meier

Accumulating statistics have shown that liver cancer causes the second highest mortality rate of cancer-related deaths worldwide, of which 80% is hepatocellular carcinoma (HCC). Given the underlying molecular mechanism of HCC pathology is not fully understood yet, identification of reliable predictive biomarkers is more applicable to improve patients’ outcomes. The results of principal component analysis (PCA) showed that the grouped data from 1557 samples in Gene Expression Omnibus (GEO) came from different populations, and the mean tumor purity of tumor tissues was 0.765 through the estimate package in R software. After integrating the differentially expressed genes (DEGs), we finally got 266 genes. Then, the protein-protein interaction (PPI) network was established based on these DEGs, which contained 240 nodes and 1747 edges. FOXM1 was the core gene in module 1 and highly associated with FOXM1 transcription factor network pathway, while FTCD was the core gene in module 2 and was enriched in the metabolism of amino acids and derivatives. The expression levels of hub genes were in line with The Cancer Genome Atlas (TCGA) database. Meanwhile, there were certain correlations among the top ten genes in the up- and downregulated DEGs. Finally, Kaplan–Meier curves and receiver operating characteristic (ROC) curves were plotted for the top five genes in PPI. Apart from CDKN3, the others were closely concerned with overall survival. In this study, we detected the potential biomarkers and their involved biological processes, which would provide a new train of thought for clinical diagnosis and treatment.

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Prognostic Significance and Immune Infiltration of Microenvironment‐related Signatures in Pancreatic Cancer

10.21203/rs.3.rs-60885/v1 ◽

2020 ◽

Author(s):

Qian Lu ◽

Yu Zhang ◽

Weihong Gu ◽

Xinrong Ji ◽

Zhong Chen

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Immune Cell ◽

Differential Expression Analysis ◽

Prognostic Significance ◽

Ductal Adenocarcinoma ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Tumor Tissues ◽

Cox Analysis

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal and most aggressive types of malignancies and accounts for the vast majority of Pancreatic Cancer (PC). Numerous studies have reported that the tumor microenvironment (TME) was significantly correlated with the oncogenesis, progress, and prognosis of various malignancies. Therefore, mining of TME-related genes is reasonably important to improve the overall survival (OS) of patients with PDAC. Methods: The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to identify differential expressed genes (DEGs). Functional and pathway enrichment analyses, protein–protein interaction (PPI) network construction and module analysis, overall survival analysis and tumor immune estimation resource (TIMER) database analysis were then performed on DEGs. Results: Data analysis indicated that higher immune scores were correlated with better overall survival (P = 0.033). Differential expression analysis obtained 90 intersection genes influencing both stromal and immune scores. Among these intersection genes, CA9, EBI3, SPOCK2, WDFY4, CD1D and CCL22 were significantly correlated with OS in PDAC patients. Moreover, multivariate Cox analysis revealed that CA9, SPOCK2 and CD1D were the most significant prognostic genes, and were closely correlated with immune infiltration in TCGA cohort. Further analysis indicated that CD1D were significantly related with immune cell biomarkers for PDAC patients. Conclusions: In summary, our findings provide a more comprehensive insight into TME and show a list of prognostic immune associated genes in PDAC. However, further studies on these genes need to be performed to gain additional understanding of the association between TME and prognosis in PDAC.

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Development of a Ferroptosis-Related lncRNA Signature to Predict the Prognosis and Immune Landscape of Bladder Cancer

Disease Markers ◽

10.1155/2021/1031906 ◽

2021 ◽

Vol 2021 ◽

pp. 1-22

Author(s):

Ranran Zhou ◽

Jingjing Liang ◽

Hu Tian ◽

Qi Chen ◽

Cheng Yang ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Model ◽

Assessment Model ◽

Chemotherapy Sensitivity ◽

Immune Infiltration ◽

Differential Coexpression ◽

Prognostic Assessment ◽

Kaplan Meier ◽

Cox Analysis ◽

Tight Correlation

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity.

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Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment

Frontiers in Oncology ◽

10.3389/fonc.2021.633462 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bo Fan ◽

Alradhi Mohammed ◽

Yuanbin Huang ◽

Hong Luo ◽

Hongxian Zhang ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Case Control Study ◽

Meta Analysis ◽

Case Control ◽

Female Patients ◽

Kaplan Meier ◽

History Of ◽

The Impact ◽

Control Study

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

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DOCK4 Correlated with Immune Infiltration is a Valuable Prognostic Biomarker in Stomach Adenocarcinoma.

10.21203/rs.3.rs-1020016/v1 ◽

2021 ◽

Author(s):

Yi Lu ◽

Xi Jia Yu ◽

Ping Qiu Dong ◽

Yan Du ◽

Zheng Liang

Keyword(s):

Negative Impact ◽

Small Gtpase ◽

Marker Genes ◽

Nucleotide Exchange ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Kaplan Meier ◽

Nucleotide Exchange Factor ◽

Stomach Adenocarcinoma

Abstract Background:Dedicator for cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, the mechanisms involved in immune infiltration in STAD (stomachadenocarcinoma) remain unclear. Methods: The UALCAN database was used to analyze the expression of the DOCKfamily, and the Kaplan-Meier plotter and GEPIA databases were used to assess the prognostic value of the DOCK family in STAD. Furthermore,the correlation between DOCK4 expression withtumor immune infiltration and the expression of related immune marker genes in STAD was explored using TIMER and GEPIA websites. Subsequently, the relationship between DOCK4 expression and clinical characteristics was verified using the UALCAN database. Finally, the mutation of DOCK4 was analyzed via TIMER2.0 and cBioPortal databases. And the protein-protein interaction(PPI) networks of DOCK4 were constructed using GeneMANIA and STRING websites.Results: DOCK4 was finally screened out, and its expression in tumors was significantly evaluated relative to paracancerous tissues and had a negative impact on the prognosis of patients with STAD.DOCK4 was found significantly related to tumor immune infiltration in STAD.Conclusions:In summary, DOCK4 is a potential regulator of the recruitment and regulation of immune infiltrating cells, thus becoming a valuable prognosticbiomarker in STAD.

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CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle

Experimental Biology and Medicine ◽

10.1177/15353702211049149 ◽

2021 ◽

pp. 153537022110491

Author(s):

Min-Hua Rong ◽

Jian-Di Li ◽

Lu-Yang Zhong ◽

Yu-Zhen Huang ◽

Juan Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Overall Survival ◽

Dna Replication ◽

Early Stage ◽

Cyclin B1 ◽

Survival Outcomes ◽

Clinicopathologic Characteristics ◽

Protein Protein Interaction ◽

Cox Analysis

In our studies, cyclin B1 ( CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

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Mining TCGA database for gene expression in ovarian serous cystadenocarcinoma microenvironment

PeerJ ◽

10.7717/peerj.11375 ◽

2021 ◽

Vol 9 ◽

pp. e11375

Author(s):

Youzheng Xu ◽

Yixin Xu ◽

Chun Wang ◽

Baoguo Xia ◽

Qingling Mu ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Strong Predictor ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Poor Overall Survival ◽

Protein Protein Interaction ◽

Serous Cystadenocarcinoma ◽

Kaplan Meier ◽

Limma Package

Background Ovarian cancer is one of the leading causes of female deaths worldwide. Ovarian serous cystadenocarcinoma occupies about 90% of it. Effective and accurate biomarkers for diagnosis, outcome prediction and personalized treatment are needed urgently Methods Gene expression profile for OSC patients was obtained from the TCGA database. The ESTIMATE algorithm was used to calculate immune scores and stromal scores of expression data of ovarian serous cystadenocarcinoma samples. Survival results between high and low groups of immune and stromal score were compared and differentially expressed genes (DEGs) were screened out by limma package. The Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the protein-protein interaction (PPI) network analysis were performed with the g:Profiler database, the Cytoscape and Search Tool for the Retrieval of Interacting Genes (STRING-DB). Survival results between high and low immune and stromal score groups were compared. Kaplan-Meier plots based on TCGA follow up information were generated to evaluate patients’ overall survival. Results Eighty-six upregulated DEGs and one downregulated DEG were identified. Three modules, which included 49 nodes were chosen as important networks. Seven DEGs (VSIG4, TGFBI, DCN, F13A1, ALOX5AP, GPX3, SFRP4) were considered to be correlated with poor overall survival. Conclusion Seven DEGs (VSIG4, TGFBI, DCN, F13A1, ALOX5AP, GPX3, SFRP4) were correlated with poor overall survival in our study. This new set of genes can become strong predictor of survival, individually or combined. Further investigation of these genes is needed to validate the conclusion to provide novel understanding of tumor microenvironment with ovarian serous cystadenocarcinoma prognosis and treatment.

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The Expression of LIMK1 is Related to the Poor Prognosis and Immune Function of Hepatocellular Carcinoma

10.21203/rs.3.rs-910480/v1 ◽

2021 ◽

Author(s):

Yisheng Peng ◽

Jun Fan ◽

Gang Zhu ◽

Shunde Tan ◽

Jianfei Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Function ◽

Poor Prognosis ◽

Immune Cell ◽

Tnm Staging ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Normal Tissues ◽

The Poor ◽

Kaplan Meier

Abstract Background: According to reports, LIMK1 may have the effect of promoting tumor progression. However, the effect of the expression of LIMK1 on the healing of patients with hepatocellular carcinoma and its effect on the immune function are still not clear. Therefore, we analyzed the effect of LIMK1 on the healing of patients with hepatocellular carcinoma and its correlation with immunity through bioinformatics analysis.Methods: Download the transcriptional expression profile of LIMK1 in hepatocellular carcinoma tissues and normal tissues in TCGA, and study its expression in hepatocellular carcinoma. Study the expression of LIMK1 in hepatocellular carcinoma through CPTAC and HPA database. The Kaplan-Meier method was used to evaluate the effect of LIMK1 expression on the survival of patients with hepatocellular carcinoma. Use the STRING database to construct a protein-protein interaction (PPI) network. Use the "ClusterProfiler" package for feature-rich analysis. Use TISIDB database and Xiantao platform to study the relationship between LIMK1 mRNA expression and immune infiltration.Results: The expression of LIMK1 in hepatocellular carcinoma tissues was significantly up-regulated. Increased expression of LIMK1 mRNA is related to high TNM staging. In the ROC curve, when the cut-off level is 1.813, the sensitivity and specificity of LIMK1 to distinguish hepatocellular carcinoma from adjacent controls are 80.7% and 86%, respectively.The Kaplan-Meier curve shows that the higher the expression of LIMK1, the worse the survival of patients with hepatocellular carcinoma (42.2 months vs. 70 months, P = 0.001). Correlation analysis studies have shown that the expression of LIMK1 mRNA in hepatocellular carcinoma is related to immune cell infiltration.Conclusion: Up-regulation of LIMK1 may affect the survival rate and immune invasion of hepatocellular carcinoma. Studies have shown that LIMK1 may be related to the poor prognosis of hepatocellular carcinoma, and has a certain relationship with the immune infiltration of hepatocellular carcinoma.

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ITGB2 as a Novel Biomarker Correlating With Prognosis and Immune Infiltrates in Ovarian Cancer

10.21203/rs.3.rs-263949/v1 ◽

2021 ◽

Author(s):

chanyuan li ◽

Ting Wan ◽

Ting Deng ◽

Junya Cao ◽

He Huang ◽

...

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Protein Interaction ◽

Ppi Network ◽

Hub Genes ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Background: Epithelial ovarian cancer is nowadays one of the malignancies in women, this study aimed to identify novel biomarkers to predict prognosis and immunotherapy efficacy.Methods: The differentially expressed genes (DEGs) obtained from online database Gene Expression Omnibus (GEO)were screened via GEO2R and Venn diagram software, gene enrichment was analysed by Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG), then protein protein interaction(PPI)network and Cytoscape software were used to confirm the genes closely related to ovarian cancer. Survival analysis of hub genes were obtained from Kaplan–Meier plotter, with their differential expression in specimen validated by Gene Expression Profiling Interactive Analysis (GEPIA) and an integrated repository portal for tumor-immune system interactions (TISIDB). Finally, we used the Tumor Immune Estimation Resource 2.0 (TIMER2.0) and application Estimate the Proportion of Immune and Cancer cells (EPIC) to search the immune infiltration characteristics of the genes.Results: 355 DEGs between epithelial ovarian cancer and normal ovarian tissue were screened out. These DEGs were associated with extracellular exosome, bicellular tight junction and cell-cell junction, and remarkably enriched in molecules of cell adhesion and leukocyte transendothelial migration activity. Ten hub genes were identified via protein protein interaction (PPI) network: PTAFR, HLA-DRA, OAS2, OAS3, PTPN6, LYN, VAMP8, IRF6, ITGB2, CD47. Furthermore, the Kaplan–Meier plotter was conducted, overexpression of four genes was positively connected to poor prognosis in ovarian cancer:OAS2, OAS3, ITGB2, CD47,which were also correlated with immune infiltrates in ovarian cancer and had the highest degree of correlation with tumor associated macrophages (TAMs) infiltration, among which ITGB2 was highly correlated with TAMs infiltration level.Conclusion: ITGB2, OAS2, OAS3, and CD47 are upregulated with unfavorable prognosis in ovarian cancer, and ITGB2 may act as a novel prognostic biomarker with immune infiltration values.

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A Poliovirus Receptor (CD155)-Related Risk Signature Predicts the Prognosis of Bladder Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.660273 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cong Luo ◽

Wenrui Ye ◽

Jiao Hu ◽

Belaydi Othmane ◽

Huihuang Li ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

World Health ◽

Who Grade ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

Poliovirus Receptor

BackgroundBladder cancer is an aggressive and heterogeneous disease associated with high morbidity and mortality. And poliovirus receptor (PVR or CD155) played crucial roles in tumor immune microenvironment and cancer development. However, their association remains obscure.MethodsA total of 797 patients from TCGA and GEO databases were employed in our study, in which 285 cases were set as the training cohort and 512 were defined as the validation cohort. Our own Xiangya cohort with 57 samples was also used for the validation. Survival differences were evaluated by Kaplan-Meier analysis between groups. The immune infiltration was evaluated by ESTIMATE, TIMER, and CIBERSORT algorithms. The risk signature was constructed by LASSO Cox regression analysis. And a nomogram model was generated subsequent to the multivariate Cox proportional hazards analysis to predict 3- and 5-year survival of patients with bladder cancer.ResultsPVR was overexpressed across various cancers including bladder cancer and related to poorer overall survival in bladder urothelial carcinoma (BLCA). Samples with higher World Health Organization (WHO) grade or higher tumor stage tended to express higher level of PVR. And PVR-related genes were involved in several immune processes and oncological pathways. When the patients were divided into low- and high-risk groups based on their risk scores, we found that patients in the high-risk group had shorter overall survival time. Besides, samples with high risk were consistently correlated with tumor hallmarks and higher abundance of immune infiltration. Additionally, chemotherapy showed potent efficacy in high-risk group. Moreover, a nomogram including clinicopathologic features and the established risk signature could predict 3- and 5-year survival in patients with bladder cancer.ConclusionOur study revealed that PVR was overexpressed and related to poor prognosis in bladder cancer. A risk signature and nomogram model based on PVR-related genes could predict the prognosis and therapeutic efficacy and were also associated with the immune infiltration in bladder cancer.

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