GNG5 is a Novel Oncogene Associated with Poor Prognosis in Glioma Patients

Abstract Background: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 expression and glioma prognosis and to identify a new biomarker for the diagnosis and treatment of gliomas.Methods: We used datasets from databases including TCGA and GEO, and results from GEPIA, RT-qPCR, and HPA to determine the expression of GNG5 in glioma. Based on datasets obtained from the CGGA database, we identified the correlation between GNG5 expression and multiple molecular and clinical features as well as clinical prognosis using a variety of analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in gliomas and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment.Results: A total of 1826 glioma related datasets were used in our study, including sequencing data, microarray data, and RT-qPCR data. We found that GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA analysis revealed the potential signaling pathways involved in GNG5 function in gliomas, such as ECM-receptor interaction and the toll-like receptor signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma, such as B cell, macrophage, and dendritic cells.Conclusions: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

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GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma

10.21203/rs.3.rs-49192/v2 ◽

2021 ◽

Author(s):

Wang Zhang ◽

Zhendong Liu ◽

Binchao Liu ◽

Miaomiao Jiang ◽

Shi Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Clinical Data ◽

Poor Prognosis ◽

Glioma Cells ◽

Diagnosis And Treatment ◽

And Migration ◽

The Relationship ◽

Proliferation And Migration

Abstract Background: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas.Methods: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells.Results: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration.Conclusions: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

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GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma

Cancer Cell International ◽

10.1186/s12935-021-01935-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wang Zhang ◽

Zhendong Liu ◽

Binchao Liu ◽

Miaomiao Jiang ◽

Shi Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Clinical Data ◽

Poor Prognosis ◽

Glioma Cells ◽

Diagnosis And Treatment ◽

And Migration ◽

The Relationship ◽

Proliferation And Migration

Abstract Background Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas. Methods We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells. Results GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration. Conclusions Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

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The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

10.21203/rs.3.rs-31174/v1 ◽

2020 ◽

Author(s):

Xiaohong Hou ◽

Guiyin Zhou ◽

Yinchun Fan ◽

Qiang Zhang ◽

Chengming Xiang ◽

...

Keyword(s):

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Checkpoint Inhibitors ◽

Enrichment Analysis ◽

R Package ◽

High Expression ◽

Sequencing Data ◽

Mesenchymal Transition ◽

Patient Prognosis

Abstract Background Glioblastoma (GBM) is one of the most malignant tumors that can afflict the central nervous system. Previous studies have observed that there are individual differences in the treatment response of immune checkpoint inhibitors in glioblastoma. This study’s aim is to ascertain the factors that may affect the efficacy of immunosuppressant therapy. Methods The clinical data of this study were obtained from a public database. Then, the data was analyzed and processed by R software and corresponding R package. To verify the results of the analysis, information was gathered from 89 GBM patients in our hospital and thereafter the corresponding paraffin sections were stained and quantitatively analyzed by immunohistochemistry. Results From the analysis, it was observed that both CD276 and HAVCR2 were significantly overexpressed in GBM and could be associated with patient prognosis. The analysis of single cell RNA sequencing data and GBM data analysis found an immune subtype with poor prognosis. Further analysis found that the high expression of CD276, HAVCR2 and CD163 was closely related to epithelial-mesenchymal transition (EMT) and could affect the patient prognosis of PD-L1 high expression. GSVA enrichment analysis showed that CD276, HAVCR2 and CD163 might induce EMT by JAK-STAT3 signaling pathway, and RUNX1 and IKZF1 might be transcription factors that regulate CD276/HAVCR2 high expression. Conclusions We found an immune subtype with poor prognosis of GBM, the high expression of CD276, HAVCR2 and CD163 with EMT are closely related and may be one of the factors affecting the efficacy of Anti-PD-L1.

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Screening and Identification of Key Biomarkers in Breast Cancer with Brain Metastasis: Evidence from Bioinformatic Analysis

10.21203/rs.3.rs-38542/v1 ◽

2020 ◽

Author(s):

tao ming Shao ◽

zhi yang Hu ◽

wen wei Li ◽

long yun Pan

Keyword(s):

Breast Cancer ◽

Protein Interactions ◽

Poor Prognosis ◽

Target Genes ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Hub Genes ◽

Clinical Prognosis ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Purpose. Breast cancer (BC) has a poor prognosis when brain metastases (BM) occur, and the treatment effect is limited. In this study, we aim to identify representative candidate biomarkers for clinical prognosis of patients with BM and explore the mechanisms underlying the progression of BC.Methods. Herein, we examined the Microarray datasets (GSE125989) obtained from the Gene Expression Omnibus database to find the target genes in BC patients with BM. We employed the GEO2R tool to filter the differentially expressed genes (DEGs) that participate in primary BC and BC with BM. Subsequently, using the DAVID tool, we conducted an enrichment analysis with the screened DEGs based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional annotation. The STRING database was employed to analyze the protein-protein interactions of the DEGs and visualized using Cytoscape software. Lastly, the Kaplan-Meier plotter database was employed to determine the prognostic potential of hub genes in BC.Results. We screened out 311 upregulated DEGs and 104 downregulated DEGs. The enrichment analyses revealed that all the DEGs were` enriched in the biological process of extracellular matrix organization, cell adhesion, proteolysis, collagen catabolic process and immune response. The significant enrichment pathways were focal adhesion, protein absorption and digestion, ECM-receptor interaction, PI3K-Akt signalling pathway, and Pathways in cancer. The top ten hub nodes screened out included FN1, VEGFA, COL1A1, MMP2, COL3A1, COL1A2, POSTN, DCN, BGN and LOX. The Kaplan-Meier plotter results showed that the three hub genes (FN1, VEGFA and DCN) are candidate biomarkers for clinical prognosis of patients with BM.Conclusion. we identified seven genes related to poor prognosis in BCBM. FN1, VEGFA and DCN can be considered as potential prognostic markers for BCBM. Meantime, COL1A1, POSTN, BGN and LOX may be linked to the distant transformation of BC.

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Epigenetic Signaling of Cancer Stem Cells During Inflammation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.772211 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zaoqu Liu ◽

Yuqing Ren ◽

Lingfang Meng ◽

Lifeng Li ◽

Richard Beatson ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Malignant Tumors ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Tumor Treatment ◽

Smad Pathway ◽

The Relationship

Malignant tumors pose a great challenge to human health, which has led to many studies increasingly elucidating the tumorigenic process. Cancer Stem Cells (CSCs) have profound impacts on tumorigenesis and development of drug resistance. Recently, there has been increased interest in the relationship between inflammation and CSCs but the mechanism underlying this relationship has not been fully elucidated. Inflammatory cytokines produced during chronic inflammation activate signaling pathways that regulate the generation of CSCs through epigenetic mechanisms. In this review, we focus on the effects of inflammation on cancer stem cells, particularly the role of signaling pathways such as NF-κB pathway, STAT3 pathway and Smad pathway involved in regulating epigenetic changes. We hope to provide a novel perspective for improving strategies for tumor treatment.

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Identification of Therapeutic Targets and Prognostic Biomarkers Among CC Chemokines in the Pancreatic Adenocarcinoma Microenvironment

10.21203/rs.3.rs-736019/v1 ◽

2021 ◽

Author(s):

Xinyuan Liu ◽

Qi Zhang ◽

Tao Mao ◽

Congcong Min ◽

Jing Guo ◽

...

Keyword(s):

T Cells ◽

Pancreatic Adenocarcinoma ◽

Immune Cells ◽

Poor Prognosis ◽

Therapeutic Potential ◽

Malignant Tumors ◽

Therapeutic Targets ◽

Receptor Interaction ◽

Transcriptional Level ◽

Cc Chemokines

Abstract Pancreatic adenocarcinoma (PAAD) as one of the most aggressive and lethal malignant tumors is correlated with increased morbidity and mortality. Tumorigenesis, growth, and metastasis are affected by various cytokines. Among them, CC chemokines can modulate the infiltration of immune cells and recruit cancer-associated immune cells, which play an important role in the inhibition of tumor immunity and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data on the basis of ONCOMINE database, GEPIA, LinkedOmics, cBioPortal, GeneMANIA, UALCAN, jvenn, DAVID 6.8, TRRUST, TIMER, and TISIDB. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS), and patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The functions of the aberrantly expressed CC chemokines were mainly correlated with the cytokine-cytokine receptor interaction, chemokine signaling pathway, inflammatory response, and immune response. Our study shows that the key transcription factors for CC chemokines are RELA and NF-κB1. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. Taken together, our study indicated the interaction between CC chemokines and PAAD and clarified the value of CC chemokines as potential therapeutic targets as well as prognostic markers for PAAD.

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High Expression of Mitochondrial Autophagy-Related Gene FUNDC1 is Associated with Poor Prognosis of Colon Cancer and Defective Immune Cell Infiltration

10.21203/rs.3.rs-705751/v1 ◽

2021 ◽

Author(s):

Yu Guo ◽

Jian Shi ◽

Shuang Wang ◽

Zeyun Zhao ◽

An Shang ◽

...

Keyword(s):

Colon Cancer ◽

Poor Prognosis ◽

Immune Cell ◽

Univariate Analysis ◽

Cell Infiltration ◽

Clinicopathological Parameters ◽

Immune Cell Infiltration ◽

Sequencing Data ◽

The Poor ◽

The Relationship

Abstract Background: Mitochondrial dysfunction is related to the occurrence and development of many diseases. FUNDC1 has attracted attention as a receptor related to mitochondrial autophagy. Colorectal cancer is the fourth most commonly diagnosed cancer. This article uses bioinformatics analysis to study the relationship between FUNDC1 and immune cell infiltration and prognosis of colon cancer. Methods: The RNA sequencing data and detailed clinical prognostic information resources of 478 COAD samples in the TCGA database were included in the study. Two data sets (GSE37364, GSE110224) from the GEO database were selected for verification. Using Kaplan - Meier curves, univariate analysis and multivariate survival analysis to assess the relationship FUNDC1 level of expression and clinicopathological parameters and overall survival. The protein-protein interaction network of FUNDC1 was constructed by String and GeneMANIA databases. Screen the genes co-expressed with FUNDC1 in Oncomine and GEPIA. And use the TIMER database and GEPIA to explore the relationship between FUNDC1 and immune cell infiltration and surface markers. Results: FUNDC1 is obviously highly expressed in tumor samples and is related to the poor prognosis of patients. Univariate and multivariate analysis showed that FUNDC1 was related to advanced TNM staging. FUNDC1 mainly interacts with mitochondrial autophagy-related proteins. FUNDC1 is related to immune infiltration and mainly affects CD8+ T cells and macrophages. Conclusion: The research has proved that FUNDC1 is closely related to the infiltration of tumor microenvironment immune cells in COAD samples and to the poor prognosis of COAD patients, which may provide new treatment ideas and targets.

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Screening and identification of key biomarkers in breast cancer with brain metastasis: Evidence from bioinformatic analysis

10.21203/rs.3.rs-36118/v1 ◽

2020 ◽

Author(s):

Tao Ming Shao ◽

Zhi Yang Hu ◽

Wen Wei Li ◽

Long Yun Pan

Keyword(s):

Breast Cancer ◽

Protein Interactions ◽

Poor Prognosis ◽

Target Genes ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Hub Genes ◽

Clinical Prognosis ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Purpose. Breast cancer (BC) has a poor prognosis when brain metastases (BM) occur, and the treatment effect is limited. In this study, we aim to identify representative candidate biomarkers for clinical prognosis of patients with BM and explore the mechanisms underlying the progression of BC.Methods. Herein, we examined the Microarray datasets (GSE125989) obtained from the Gene Expression Omnibus database to find the target genes in BC patients with BM. We employed the GEO2R tool to filter the differentially expressed genes (DEGs) that participate in primary BC and BC with BM. Subsequently, using the DAVID tool, we conducted an enrichment analysis with the screened DEGs based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional annotation. The STRING database was employed to analyze the protein-protein interactions of the DEGs and visualized using Cytoscape software. Lastly, the Kaplan-Meier plotter database was employed to determine the prognostic potential of hub genes in BC.Results. We screened out 311 upregulated DEGs and 104 downregulated DEGs. The enrichment analyses revealed that all the DEGs were` enriched in the biological process of extracellular matrix organization, cell adhesion, proteolysis, collagen catabolic process and immune response. The significant enrichment pathways were focal adhesion, protein absorption and digestion, ECM-receptor interaction, PI3K-Akt signalling pathway, and Pathways in cancer. The top ten hub nodes screened out included FN1, VEGFA, COL1A1, MMP2, COL3A1, COL1A2, POSTN, DCN, BGN and LOX. The Kaplan-Meier plotter results showed that the three hub genes (FN1, VEGFA and DCN) are candidate biomarkers for clinical prognosis of patients with BM.Conclusion. we identified seven genes related to poor prognosis in BCBM. FN1, VEGFA and DCN can be considered as potential prognostic markers for BCBM. Meantime, COL1A1, POSTN, BGN and LOX may be linked to the distant transformation of BC.

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Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis

Journal of Oncology ◽

10.1155/2021/9951010 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Qingling Kong ◽

Guangcai Li ◽

Gang Yin ◽

Kun Li ◽

Dongqing Zhang ◽

...

Keyword(s):

Esophageal Cancer ◽

Noncoding Rna ◽

Poor Prognosis ◽

Regulatory Mechanism ◽

Malignant Tumors ◽

Luciferase Reporter ◽

Migration And Invasion ◽

The Relationship ◽

Competitive Endogenous Rna

Background. Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. Materials and Methods. RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. Results. Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. Conclusions. WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.

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