scholarly journals Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis

2018 ◽  
Vol 45 (5) ◽  
pp. 1731-1746 ◽  
Author(s):  
Erbao Chen ◽  
Xuan Qin ◽  
Ke Peng ◽  
Xiaojing Xu ◽  
Wei Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Survival Data ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Tumor Development ◽  
Mrna Levels ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Precision Therapy ◽  
Kaplan Meier Plotter

Background/Aims: Breast cancer is a common cause of cancer mortality throughout the world. The cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC is one of four chemokine families involved in mediating survival, angiogenesis, and immunosensitization by chemoattracting leukocytes, and it incentivizes tumor cell growth, invasion and metastasis in the tumor microenvironment. However, the differential expression profiles and prognostic values of these chemokines remains to be elucidated. Methods: In this study, we compared transcriptional CXC chemokines and survival data of patients with breast carcinoma (BC) using the ONCOMINE dataset, Kaplan-Meier Plotter, TCGA and cBioPortal. Results: We discovered increased mRNA levels for CXCL8/10/11/16/17, whereas mRNA expression of CXCL1/2/3/4/5/6/7/12/14 was lower in BC patients compared to non-tumor tissues. Kaplan-Meier plots revealed that high mRNA levels of CXCL1/2/3/4/5/6/7/12/14 correlate with relapse-free survival (RFS) in all types of BC patients. Conversely, high CXCL8/10/11 predicted worse RFS in BC patients. Significantly, high transcription levels of CXCL9/12/13/14 conferred an overall survival (OS) advantage in BC patients, while high levels of CXCL8 demonstrated shorter OS in all BC sufferers. Conclusions: Integrative bioinformatics analysis suggests that CXCL8/12/14 are potential suitable targets for precision therapy in BC patients compared to other CXC chemokines.

scholarly journals Identification of Prognostic Biomarkers Among DAAM1, FHOD1,FMN2 and INF2 in Breast Cancer Patients

2021 ◽  
Author(s):  
Yin-Hai Dai ◽  
Fuping Li ◽  
Wei-Jie Kong ◽  
Xue-Qin Zhang ◽  
Mao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Survival Data ◽  
Mrna Level ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Migration Of Cells ◽  
Kaplan Meier Plotter

Abstract Background:The formin family proteins are main regulators of actin filaments, which play a crucial role in the migration of cells and carcinogenesis.The specific functions of the formin family proteins in breast cancer still remain unknown.To dissolve this problem,we selected four formin proteins including DAAM1,FHOD1, FMN2 and INF2 and investigated their mRNA expression and survival data in BC(breast carcinoma) patients using diverse databases.Methods:we used these databases including Oncomine, Ualcan, GEPIA 2,HumanProtein Atlas,Metascape,Kaplan-Meier plotter,cBioPortal and TIMER and the software of Cytoscape in our study.Results:DAAM1 and FMN2 were lowly expressed in BC tissues,while FHOD1 and INF2 were highly expressed in BC tissues.The expression levels of DAAM1, FMN2 and FHOD1 were relevant to major subclasses,and the mRNA level of FHOD1 was related to cancer staging.Moreover,High mRNA levels of FHOD1 and INF2 were relevant to poorer prognosis of BC patients,while low mRNA level of DAAM1 was correlated with better prognosis.we also found that there were significant associations between the expressions of DAAM1,FHOD1,FMN2 and INF2 and six types of infiltrated immune cells(B Cells,CD4+T cells,CD8+T cells, neutrophil,macrophage,and dendritic cell).Conclusions:our study indicated that FHOD1 and INF2 were potential biomarkers to identify short survival of BC patients,FMN2 was potential prognostic marker to suggest favorable survival of BC patients.

scholarly journals Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
Huiying Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatics Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Research Progress ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

scholarly journals Identification of key survival genes of the tumor microenvironment and immune infiltration in head and neck squamous cell carcinoma

2021 ◽  
Author(s):  
Min Wang ◽  
Tao Lu ◽  
Yanshi Li ◽  
Min Pan ◽  
Zhihai Wang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Tumor Microenvironment ◽  
Head And Neck ◽  
Stromal Cells ◽  
Survival Data ◽  
Expression Profiles ◽  
Critical Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier

Abstract Background: Head and neck cancer (HNC) are highly aggressive solid tumors with poor prognoses. The tumor microenvironment (TME) plays a critical role in angiogenesis, invasion, and metastasis of HNC. In the TME, immune and stromal cells influence tumor initiation, response, and therapy. Our study aimed to evaluate the progression and prognosis of HNC by analyzing the key genes involved in immunization and stromal cells. Methods: Gene expression profiles, demographics, and survival data were downloaded from the TCGA database. Patients with HNC were divided into high immune/stromal score groupss or low immune/stromal score groups based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified via functional enrichment analysis and protein-protein interaction networks, and survival analysis based on DEGs was also performed.Results: A total of 522 patients with HNC were enrolled for analysis. The average age was 60.87, and one-third of the patients were HPV-positive. Kaplan-Meier survival analysis showed that patients' median survival time in the low-score group was shorter than that of the high-score group (625 vs. 680 days, log-rank, p = 0.1716). According to immune scores, 925 genes were upregulated, and 72 genes were downregulated in the high-score group compared with the low-score group. Top Gene Ontology terms identified that T-cell costimulation, regulation of immune response, and the external side of the plasma membrane were the most involved pathways. Moreover, Kaplan-Meier analysis revealed that 480 DEGs were upregulated in the high-immune scores group, and a total of 126 DEGs were significantly associated with poor survival. Besides, we identified the hub genes of DEGs through protein-protein interactions and found that PTPRC, CD247, and CD4 are associated with immune infiltration and all-cause mortality.Conclusions: We identified a series of TME‐related genes significantly associated with overall mortality; this information is crucial for further understanding the role of TME and immune infiltration in the prognosis of HNC.

Identification Of The Molecular Targets And Immunophenotype Of Gastric Cancer By Bioinformatics Analysis

2020 ◽  
Author(s):  
Tao Yang ◽  
KeGang Zhang ◽  
Rui Xu ◽  
Junhao You ◽  
Fang Li
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Expression Profiles ◽  
Molecular Characteristics ◽  
Survival Prediction ◽  
P53 Signaling ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
P53 Signaling Pathway ◽  
Kaplan Meier Plotter

Abstract Background: Gastric cancer (GC) is the most lethal tumor of gastrointestinal tract worldwide. Despite advances in various therapies, the prognosis of GC remains poor. Moreover, only a small fraction of GC patients benefit from immunotherapy. Therefore, it is urgent to deeply understand the molecular characteristics and immunophenotype of GC. Methods: We analyzed the gene expression profile of GSE118916 from GEO database, including the mRNA expression profiles of 15 pairs of GC tumor and adjacent non-tumor tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online website DAVID. And then the survival prediction values of the top 10 up-regulated genes were analyzed using Kaplan–Meier plotter database. Finally, the immune cells infiltration was analyzed using CIBERSORT online tool.Results: A total of 1156 DEGs were identified, including 633 up-regulated genes and 523 down-regulated genes. The up-regulated genes were mainly enriched in cell adhesion, proliferation, migration and inflammation response. In addition, the up-regulated genes were significantly enriched in acid metabolism, complement and coagulation cascades, cell adhesion and p53 signaling pathway, which were all significant in tumor progression, relapse and metastasis. In addition, the up-regulated genes CTSL and PIEZO1 were associated with poor prognosis in GC patients. Moreover, a unique immune-suppressive microenvironment was identified in GC tissues. Conclusions: CTSL and PIEZO1 might be potential biomarkers and therapeutic targets in GC patients.

scholarly journals Bioinformatics Analysis and Insights for the Role of COMMD7 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Jing Li ◽  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatics Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Research Progress ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

scholarly journals Diagnostic, Therapeutic, and Prognostic Value of the Thrombospondin Family in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Lu ◽  
Xianhe Kong ◽  
Weijie Zhong ◽  
Minhui Hu ◽  
Chujun Li
Keyword(s):  
Gastric Cancer ◽  
Tumor Immunology ◽  
Hedgehog Signaling ◽  
Tumor Stage ◽  
Receptor Interaction ◽  
Mrna Levels ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Stage 1 ◽  
Kaplan Meier Plotter

Background: Gastric cancer (GC) is the fifth leading cancer in the world. The dysregulated expressions of the thrombospondin (THBS) family were reported to associate with GC, but their relations with tumor stage, prognosis, and correlations with tumor immunity have not been systematically reported.Methods: We used versatile public databases such as Oncomine, GEPIA, UALCAN, Kaplan–Meier Plotter, LinkedOmics, STRING, cBioPortal, TIMER, and TISIDB to analyze the expression and mutations of different THBSs in GC, along with their functional networks, survival analysis, and tumor–immune interactions.Results: The mRNA levels of THBS2, THBS4, and COMP were significantly higher in the tumor tissues; the expression levels of THBS1, THBS2, and THBS4 were higher in stages 2–4 than that of stage 1; patients with high expression of THBS1, THBS2, THBS4, and COMP had poor OS; the genes correlated with THBSs were enriched in focal adhesion, glycosaminoglycan biosynthesis, ECM-receptor interaction, and hedgehog signaling pathway; THBS1 and THBS4 expression had significant correlations with tumor purity, and all the THBSs expression correlated with macrophage and dendritic cells infiltration.Conclusions: THBS2, THBS4, and COMP were potentially diagnostic markers for GC; THBS1, THBS2, THBS4, and COMP were potentially prognostic markers for GC; investigating the relations of THBSs and tumor immunology might help in immunotherapy of GC, while more studies are needed to confirm these results.

scholarly journals DOK5 as a Prognostic Biomarker of Gastric Cancer Immunoinvasion: A Bioinformatics Analysis

2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Fengyong Luo ◽  
Zhihuai Wang ◽  
Shuai Chen ◽  
Zhenbo Luo ◽  
Gaochao Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Data ◽  
Bioinformatics Analysis ◽  
Kaplan Meier ◽  
Pathogenic Genes ◽  
Protein Group ◽  
High Level ◽  
Docking Protein ◽  
Kaplan Meier Plotter

Background. Docking protein 5 (DOK5) is a member of the docking protein group of membrane proteins and is an adapter protein involved in signal transduction. Nevertheless, the role of DOK5 expression in the prognosis of gastric cancer (GC) remains unclear. Methods. In this study, clinical prognostic parameters and survival data related to DOK5, in patients with GC, were analyzed using bioinformatics analysis comprising Oncomine and TIMER, UALCAN database, Kaplan-Meier plotter, GEPIA, GSEA, DAVID, and cBioPortal websites. Results. In our study, GC contained various DOK5 expressions, which forecasted poor survival outcomes. Moreover, our research showed that high DOK5 could predict high-level infiltration of several GC immune cells, as evidenced by M1, TAM, M2, B cell, and T cell failure. Hence, DOK5 might become a new gastric cancer biomarker and therapeutic target. In the following analysis, in order to explore the prognostic value of DOK5 in GC, more clinical trials are needed to validate our results. Conclusions. Through multiple database verifications, DOK5 was found to be part of the pathogenic genes for GC. Thus, it can change the formation and progression of tumors by acting on human immunity.

scholarly journals NITUMID: Nonnegative matrix factorization-based Immune-TUmor MIcroenvironment Deconvolution

2019 ◽  
Author(s):  
Daiwei Tang ◽  
Seyoung Park ◽  
Hongyu Zhao
Keyword(s):  
Tumor Microenvironment ◽  
Matrix Factorization ◽  
Nonnegative Matrix Factorization ◽  
Expression Profiles ◽  
Mrna Level ◽  
Nonnegative Matrix ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Supplementary Information ◽  
Mrna Levels

Abstract Motivation A number of computational methods have been proposed recently to profile tumor microenvironment (TME) from bulk RNA data, and they have proved useful for understanding microenvironment differences among therapeutic response groups. However, these methods are not able to account for tumor proportion nor variable mRNA levels across cell types. Results In this article, we propose a Nonnegative Matrix Factorization-based Immune-TUmor MIcroenvironment Deconvolution (NITUMID) framework for TME profiling that addresses these limitations. It is designed to provide robust estimates of tumor and immune cells proportions simultaneously, while accommodating mRNA level differences across cell types. Through comprehensive simulations and real data analyses, we demonstrate that NITUMID not only can accurately estimate tumor fractions and cell types’ mRNA levels, which are currently unavailable in other methods; it also outperforms most existing deconvolution methods in regular cell type profiling accuracy. Moreover, we show that NITUMID can more effectively detect clinical and prognostic signals from gene expression profiles in tumor than other methods. Availability and implementation The algorithm is implemented in R. The source code can be downloaded at https://github.com/tdw1221/NITUMID. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals High SALM3 Expression in Tumor Cells and Fibroblasts Is Correlated with Poor Prognosis in Gastric Cancer Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Liu ◽  
Xiaoli Chen ◽  
Xi Chen ◽  
Xiaobing Yang ◽  
Qingjie Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Survival Data ◽  
Proportional Hazards ◽  
Synapse Formation ◽  
Tissue Microarrays ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.

scholarly journals SLC2A5 Correlated with Immune Infiltration: A Candidate Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Jiating Su ◽  
Yushi Zheng ◽  
Fangfang Huang ◽  
Riming Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Clinical Feature ◽  
Lung Cancer Patients ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Kaplan Meier Plotter

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with a relatively poor prognosis, requiring novel therapeutic approaches. Great advances in new immunotherapy strategies have shown encouraging results in lung cancer patients. This study is aimed at elucidating the function of SLC2A5 in the prognosis and pathogenesis of LUAD by analyzing public databases. The differential expression of SLC2A5 in various tissues from Oncomine, GEPIA, and other databases was obtained, and SLC2A5 expression at the protein level in normal and tumor tissues was detected with the use of the HPA database. Then, we used the UALCAN database to analyze the expression of SLC2A5 in different clinical feature subgroups. Notably, in both PrognoScan and Kaplan-Meier plotter databases, we found a certain association between SLC2A5 and poor OS outcomes in LUAD patients. Studies based on the TIMER database show a strong correlation between SLC2A5 expression and various immune cell infiltrates and markers. The data analysis in the UALCAN database showed that the decreased promoter methylation level of SLC2A5 in LUAD may lead to the high expression of SLC2A5. Finally, we used the LinkedOmics database to evaluate the SLC2A5-related coexpression and functional networks in LUAD and to investigate their role in tumor immunity. These findings suggest that SLC2A5 correlated with immune infiltration can be used as a candidate diagnostic and prognostic biomarker in LUAD patients.

Sign in / Sign up

Export Citation Format

Share Document