scholarly journals EFNA3 Can Serve as Potential Prognostic Biomarker for Luad Patients: A Comprehensive Analysis of the Eph/Ephrin  Family

2020 ◽  
Author(s):  
Gang Hou ◽  
Mingming Deng ◽  
Run Tong ◽  
Zhe Zhang ◽  
Tao Wang ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Synaptic Function ◽  
Gene Set Enrichment Analysis ◽  
Clinical Value ◽  
Expression Levels ◽  
Diagnosis And Prognosis ◽  
Prognostic Analysis ◽  
Kaplan Meier

Abstract Background: Ephrin receptors (Eph) and their ligands called ephrins, function in various disease processes. However, the specific mechanism of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. The Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Clinical LUAD tissue was analyzed by immunohistochemistry identifying the clinical value of identifying the ephrin-A3 protein. Weighted Co-expression Network Analysis (WGCNA) and Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3.Results: EPHA10, EFNA3/4/5 and EPHB1/2 mRNA expression levels were significantly increased in LUAD. EFNB1/2 and EPHB6 expression levels were significantly decreased. Prognostic analysis showed that EFNA3, EFNB1/2, and EPHB2 expression were significant correlate with both overall survival (OS) and progression-free survival (PFS) in LUAD patients. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated as an independent risk prognosis factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. Additionally, higher expression of EFNA3 was significantly correlated with OS in pan-cancer patients.Conclusions: This study revealed the abnormal expression and prognostic value of Eph/Ephrin family members in LUAD. In addition, it is emphasized that EFNA3 may be a novel biomarker for the diagnosis and prognosis of LUAD patients.

scholarly journals EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingming Deng ◽  
Run Tong ◽  
Zhe Zhang ◽  
Tao Wang ◽  
Chaonan Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Synaptic Function ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Clinical Value ◽  
Clinical Prognosis

Abstract Background Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. Methods The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. Results In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. Conclusions In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.

scholarly journals Identification of Potential Hub Genes Related to Diagnosis and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma via Integrated Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Yuqin Tang ◽  
Yongqiang Zhang ◽  
Xun Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Diagnosis And Prognosis ◽  
Prognostic Analysis ◽  
B Virus

Hepatocellular carcinoma (HCC) is a common malignant cancer with poor survival outcomes, and hepatitis B virus (HBV) infection is most likely to contribute to HCC. But the molecular mechanism remains obscure. Our study intended to identify the candidate potential hub genes associated with the carcinogenesis of HBV-related HCC (HBV-HCC), which may be helpful in developing novel tumor biomarkers for potential targeted therapies. Four transcriptome datasets (GSE84402, GSE25097, GSE94660, and GSE121248) were used to screen the 309 overlapping differentially expressed genes (DEGs), including 100 upregulated genes and 209 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to explore the biological function of DEGs. A PPI network based on the STRING database was constructed and visualized by the Cytoscape software, consisting of 209 nodes and 1676 edges. Then, we recognized 17 hub genes by CytoHubba plugin, which were further validated on additional three datasets (GSE14520, TCGA-LIHC, and ICGC-LIRI-JP). The diagnostic effectiveness of hub genes was assessed with receiver operating characteristic (ROC) analysis, and all hub genes displayed good performance in discriminating TNM stage I patient samples and normal tissue ones. For prognostic analysis, two prognostic key genes (TOP2A and KIF11) out of the 17 hub genes were screened and used to develop a prognostic signature, which showed good potential for overall survival (OS) stratification of HBV-HCC patients. Gene Set Enrichment Analysis (GSEA) was performed in order to better understand the function of this prognostic gene signature. Finally, the miRNA–mRNA regulatory relationships of all hub genes in human liver were predicted using miRNet. In conclusion, the current study gives further insight on the pathogenesis and carcinogenesis of HBV-HCC, and the identified DEGs provide a promising direction for improving the diagnostic, prognostic, and therapeutic outcomes of HBV-HCC.

scholarly journals The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jiawei Yao ◽  
Xin Chen ◽  
Zhendong Liu ◽  
Ruotian Zhang ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Multidimensional Data ◽  
Normal Brain ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Therapy Target

Abstract Background Glioma is the most common malignant brain tumor in adults. The standard treatment scheme of glioma is surgical resection combined alternative radio- and chemotherapy. However, the outcome of glioma patients was unsatisfied. Here, we aimed to explore the molecular and biological function characteristics of GPX7 in glioma. Methods The multidimensional data of glioma samples were downloaded from Chinese Glioma Genome Atlas (CGGA). RT-qPCR method was used to identify the expression status of GPX7. Kaplan–Meier curves and Cox regression analysis were used to explore the prognostic value of GPX7. Gene Set Enrichment Analysis (GSEA) was applied to investigate the GPX7-related functions in glioma. Results The results indicated that the expression of GPX7 in glioma was higher compared to that in normal brain tissue. Univariate and multivariate Cox regression analyses confirmed that the expression value of GPX7 was an independent prognostic factor in glioma. The GSEA analysis showed that GPX7 was significantly enriched in the cell cycle pathway, ECM pathway, focal adhesion pathway, and toll-like receptor pathway. Conclusions The GPX7 was recommended as an independent risk factor for patients diagnosed with glioma for the first time and GPX7 could be potentially used as the therapy target in future. Furthermore, we attempted to explore a potential biomarker for improving the diagnosis and prognosis of patients with glioma.

scholarly journals Expression Profile and Prognostic Value of CXCR Family Members in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Yiming Shen ◽  
Chongchang Zhou ◽  
Yujie Cao ◽  
Qun Li ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Head And Neck ◽  
Expression Profile ◽  
Prognostic Value ◽  
Inflammatory Responses ◽  
Receptor Gene ◽  
Family Members ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

Abstract Background: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). Methods: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). Results: CXCRs were differentially expressed in HNSCC. As shown by Kaplan Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. Conclusions: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

scholarly journals Expression and Prognostic Analysis of Integrins in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Jun-Fu Wang ◽  
Ye Wang ◽  
Si-Wen Zhang ◽  
Ye-Yang Chen ◽  
Yue Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Diagnostic Marker ◽  
Receptor Interaction ◽  
Sequencing Data ◽  
Normal Tissues ◽  
Diagnosis And Prognosis ◽  
Prognostic Analysis ◽  
Kaplan Meier

Background. Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. Methods. GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan–Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. Results. ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT–PCR ( P < 0.001 ) and ROC ( P < 0.001 , AUC (95% CI) = 0.747 (0.641–0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. Conclusion. This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.

scholarly journals Fam20C Overexpression Predicts Poor Outcomes and is a Diagnostic Biomarker in Lower-Grade Glioma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Feng ◽  
Jinping Zhou ◽  
Lin Zhao ◽  
Xinpeng Wang ◽  
Danyu Ma ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Research Field ◽  
Gene Set Enrichment Analysis ◽  
Lower Grade ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Poor Outcomes

Glioma is a relatively low aggressive brain tumor. Although the median survival time of patients for lower-grade glioma (LGG) was longer than that of patients for glioblastoma, the overall survival was still short. Therefore, it is urgent to find out more effective molecular prognostic markers. The role of the Fam20 kinase family in different tumors was an emerging research field. However, the biological function of Fam20C and its prognostic value in brain tumors have rarely been reported. This study aimed to evaluate the value of Fam20C as a potential prognostic marker for LGG. A total of 761 LGG samples (our cohort, TCGA and CGGA) were included to investigate the expression and role of Fam20C in LGG. We found that Fam20C was drastically overexpressed in LGG and was positively associated with its clinical progression. Kaplan-Meier analysis and a Cox regression model were employed to evaluate its prognostic value, and Fam20C was found as an independent risk factor in LGG patients. Gene set enrichment analysis also revealed the potential signaling pathways associated with Fam20C gene expression in LGG; these pathways were mainly enriched in extracellular matrix receptor interactions, cell adhesion, cell apoptosis, NOTCH signaling, cell cycle, etc. In summary, our findings provide insights for understanding the potential role of Fam20C and its application as a new prognostic biomarker for LGG.

scholarly journals Downregulated ZC3H13 by miR-362-3p/miR-425-5p is Associated with Poor Prognosis and Adverse Outcomes in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
shuang wu ◽  
Shihai Liu ◽  
Yongxian Cao ◽  
Chao Geng ◽  
Peng Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Human Cancer ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Adverse Outcomes ◽  
Gene Set Enrichment Analysis ◽  
Rna Modification ◽  
Kaplan Meier

Abstract Background: Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that N6-methyladenosine (m6A) related genes plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of m6A RNA modification in HCC remains not fully determined. Previous studies identified that several m6A-related genes, especially ZC3H13, could be a high candidate as a novel biomarker and therapeutic target for hepatocellular carcinoma. In liver hepatocellular carcinoma (LIHC), the low expression of ZC3H13 was reported but the molecular reason is unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of ZC3H13 in multiple cancers. Kaplan–Meier plotter was selected to explore the prognostic value of ZC3H13. The GSCALite database was used to analyze the genetic variation of the m6A-related genes. StarBase was selected to predict and analysis of upstream miRNAs of ZC3H13. MiR-362-3p/miR-425-5p mimics and inhibitors results detected by Quantitative Real-time PCR (qPCR) analysis and western blotting. Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of ZC3H13. In addition, we investigated the relationship between ZC3H13 and tumor infiltrating immune cells (TIICs). Finally, we determined the expression correlation of ZC3H13 with biomarkers of immune cells in HCC using GEPIA database.Results: In this study, we found that ZC3H13 expression was significantly correlated with both overall survival (OS) and progression-free survival (RFS) in LIHC patients based on a comprehensive analysis of the m6A family. Our experimental results indicate that inhibiting miR-362-3p/miR-425-5p expression in the LIHC cell line significantly restored the expression of ZC3H13, which is consistent with bioinformatic studies. Further, we noticed that there is a possible relationship between ZC3H13 high expression and tumor microenvironment infiltrating immune cells.Conclusions: In conclusion, this study demonstrates that ZC3H13 is a direct target of miR-362-3p/miR-425-5p in LIHC that regulates the immune modulations in the microenvironment of LIHC.

scholarly journals High expression of PIMREG predicts poor survival outcomes and is correlated with immune infiltrates in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11697
Author(s):  
Feng Jiang ◽  
Min Liang ◽  
Xiaolu Huang ◽  
Wenjing Shi ◽  
Yumin Wang
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Background PIMREG is upregulated in multiple cancer types. However, the potential role of PIMREG in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to explore its clinical significance in LUAD. Methods Using the Cancer Genome Atlas (TCGA) databases, we obtained 513 samples of LUAD and 59 normal samples from the Cancer Genome Atlas (TCGA) databases to analyze the relationship between PIMREG and LUAD. We used t and Chi-square tests to evaluate the level of expression of PIMREG and its clinical implication in LUAD. The prognostic value of PIMREG in LUAD was identified through the Kaplan–Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to screen biological pathways and analyze the correlation of the immune infiltrating level with the expression of PIMREG in LUAD. Results PIMREG was highly expressed in patients with LUAD. Specifically, the level of PIMREG gradually increased from pathological stage I to IV. Further, we validated the higher expression of PIMREG expressed in LUAD cell lines. Moreover, PIMREG had a high diagnostic value, with an -AUC of 0.955. Kaplan–Meier survival and Cox regression analyses revealed that the high expression of PIMREG was independently associated with poor clinical outcomes. In our prognostic nomogram, the expression of PIMREG implied a significant prognostic value. Gene set enrichment analysis (GSEA) identified that the high expression PIMREG phenotype was involved in the mitotic cell cycle, mRNA splicing, DNA repair, Rho GTPase signaling, TP53 transcriptional regulation, and translation pathways. Next, we also explored the correlation of PIMREG and tumor-immune interactions and found a negative correlation between PIMREG and the immune infiltrating level of T cells, macrophages, B cells, dendritic cells (DCs) , and CD8+ T cells in LUAD. Conclusions High levels of PIMREG correlated with poor prognosis and immune infiltrates in LUAD.

scholarly journals ARID1A Upregulation Predicts Poor Survival in Patients with Liver Cancer

2021 ◽  
Author(s):  
Feng Jiang ◽  
Ke Wei ◽  
Ming Wang ◽  
Chuyan Wu
Keyword(s):  
Overall Survival ◽  
Liver Cancer ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Erbb Signaling

Abstract Objective: ARID1A has been identified as a possible biomarker for certain cancers. There is, however, some debate regarding its function in liver cancer. Methods: Associations between clinical variables and ARID1A were evaluated. Cox and Kaplan – Meier analysis were used to examine clinicalopathological factors linked to overall survival of patients with liver cancer. Gene Set Enrichment Analysis (GSEA) was conducted using the dataset of the Cancer Genome Atlas. Results: High expression of ARID1A was correlated with the gender and tumor topography (T) diagnosis of liver cancer. Patients with elevated ARID1A expression had poorer prognosis than those with low ARID1A expression. The study also showed that ARID1A was an independent risk factor for overall survival. GSEA established pathways involved in ERBB signaling, cancer, insulin signaling, mTOR signaling, MAPK signaling, VEGF signaling, Ubiquitin signaling, and Wnt signaling as differentially enriched in ARID1A-high expression liver cancer. Conclusion: ARID1A has been shown to be expressed at high rates of liver cancer and to represent a possible independent molecular marker for diagnosis and prognosis of liver cancer.

scholarly journals ARID1A Upregulation Predicts Poor Survival in Patients With Liver Cancer 

2021 ◽  
Author(s):  
Feng Jiang ◽  
Ke Wei ◽  
Ming Wang ◽  
Chuyan Wu
Keyword(s):  
Overall Survival ◽  
Liver Cancer ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Erbb Signaling

Abstract Objective: ARID1A has been identified as a possible biomarker for certain cancers. There is, however, some debate regarding its function in liver cancer. Methods: Associations between clinical variables and ARID1A were evaluated. Cox and Kaplan – Meier analysis were used to examine clinical pathological factors linked to overall survival of patients with liver cancer. Gene set enrichment analysis (GSEA) was conducted using the dataset of the cancer genome atlas(TCGA). Results: High expression of ARID1A was correlated with the gender and tumor topography (T) diagnosis of liver cancer. Patients with elevated ARID1A expression had poorer prognosis than those with low ARID1A expression. The study also showed that ARID1A was an independent risk factor for overall survival. GSEA established pathways involved in ERBB signaling, cancer, insulin signaling, mTOR signaling, MAPK signaling, VEGF signaling, Ubiquitin signaling, and Wnt signaling as differentially enriched in ARID1A-high expression liver cancer. Conclusion: ARID1A has been shown to be expressed at high rates of liver cancer and to represent a possible independent molecular marker for diagnosis and prognosis of liver cancer.

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