scholarly journals Potential Value of PRKDC as a Therapeutic Target and Prognostic Biomarker in Pan-Cancer

2021 ◽  
Author(s):  
Xiawei Yang ◽  
Xuyong Sun ◽  
Feng Yang ◽  
Liugen Lan ◽  
Ning Wen ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Prognostic Biomarker ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Rna Degradation ◽  
Gene Set Enrichment Analysis ◽  
Survival Prognosis ◽  
Potential Value ◽  
Pan Cancer

Abstract Background While PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) plays an important role in double-strand break (DSB) repair to retain genomic stability, there is still no pan-cancer analysis based on large clinical information on the relationship between PRKDC and different tumors. For the first time, this research used numerous databases to perform a pan-cancer review for PRKDC to explore the possible mechanism of PRKDC in the etiology and outcomes in various tumors. Methods PRKDC's expression profile and prognostic significance in pan-cancer were investigated based on various databases and online platforms, including TIMER2, GEPIA2, cBioPortal, CPTAC, and SangerBox. We applied the TIMER to identified the interlink of PRKDC and the immune infiltration in assorted tumors, and the SangerBox online platform was adopted to find out the relevance between PRKDC and immune checkpoint genes, TMB, and MSI in tumors. GeneMANIA tool was employed to create a Protein-Protein Interaction (PPI) analysis, gene set enrichment analysis (GSEA) was conducted to performed gene enrichment analysis. Results Overall, tumor tissue presented a higher degree of PRKDC expression than adjacent normal tissue. Meanwhile, patients with high PRKDC expression have a worse prognosis. PRKDC mutations were present in almost all TCGA tumors and might lead to a better survival prognosis. PRKDC expression level was shown a positive correlation with tumor-infiltrating immune cells (TIICs). PRKDC high expression cohorts were enriched in "cell cycle," "oocyte meiosis," and "RNA-degradation" signaling pathways. Conclusions This study revealed the potential value of PRKDC tumor immunology and as a therapeutic target and prognostic biomarker in pan-cancer.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

High UBE2T mRNA expression and its prognostic significance in Ovarian cancer: a study based on data mining

2020 ◽  
Author(s):  
Fu-Cheng Cai
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cell ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Rna Degradation ◽  
Gene Set Enrichment Analysis ◽  
Pathogenesis Related ◽  
Biologic Effect ◽  
The Difference

Abstract Background Ovarian cancer (OC) affects about 22 000 women annually in the US and ranks 5th in cancer deaths, largely due to diagnosed with advanced stage. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian cancer cases. Our study was to assess the prognostic meaningful of UBE2T expression in OC dependent on data acquired from TCGA and so as to increase further knowledge into the biological pathways involved in OC pathogenesis related to UBE2T. Methods Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression. Results The scatter plot showed the difference of UBE2T expression between normal and tumor samples ( P <0.01). So as to decide the biological interaction network of UBE2T in OC, we used to tab Network in cBioPortal and the 50 most as often altered neighbor genes of UBE2T were demonstrated utilizing Network and the most frequent alterations were HES1. The GSEA results showed that cell cycle, DNA replication, RNA degradation, some cancers, spliceosome, Huntington’s disease, oxidative phosphorylation are differentially enriched in UBE2T high expression phenotype. Cumulative survive showed that dendritic cell of immune infiltrates statistically significant ( P <0.05) of UBE2T in OC suggesting that dendritic cell significantly affecting the prognosis, it is worth more research and exploration. Conclusion Our study found that the expression of UBE2T was significantly increased in OC patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in OC, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.

scholarly journals Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Lin ◽  
Yingzhao Zhang ◽  
Zhimei Lin ◽  
Lisheng Peng
Keyword(s):  
Genome Stability ◽  
Prognostic Significance ◽  
High Mobility ◽  
Predictive Biomarkers ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cancer Pathogenesis ◽  
Tumor Mutational Burden ◽  
Clinicopathological Significance ◽  
Pan Cancer

Background: High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear.Methods: Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms.Results: HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for HMGB1 in ACC; HMGB2 in ACC, LGG, LIHC, and SKCM; and HMGB3 in ESCA. Prognostic values were also found for HMGB2 in KIRP and MESO and HMGB3 in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events.Conclusion: This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.

scholarly journals EPDR1 correlates with immune cell infiltration in hepatocellular carcinoma and can be used as a prognostic biomarker

2020 ◽  
Author(s):  
Ruochan Chen ◽  
Yiya Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Functional Analysis ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Normal Tissues

Abstract Background: Hepatocellular carcinoma (HCC) has high mortality rate and is a serious disease burden globally. Hence, identification and characterization of novel biomarkers for the diagnosis and prognosis of HCC are critically important. The protein EPDR1 (ependymin related 1) is a member of piscine brain glycoproteins and is involved in cell adhesion. This is the first study to report the expression of EPDR1 and its prognostic significance, pathological role, and association with cancer immunity in HCC.Methods: The gene expression, prognostic, and clinicopathological analyses were performed based on the data obtained from multiple transcriptome databases. Protein expression of EPDR1 in HCC was verified using human protein atlas and CPTAC databases. Co-expression network analysis using the LinkedOmics database was performed to identify genes co-expressed with EPDR1 expression. Functional analysis of the co-expressed genes, including gene set enrichment analysis was performed to identify the functional role of EPDR1. The statistical analysis was conducted in R, and the relationship between EPDR1 expression and immune cell infiltration was analyzed using TIMER and CIBERSORT resources. Results: The expression of EPDR1 was found to be significantly higher in HCC tissues than in the normal tissues and is an independent prognostic factor for the overall survival of HCC patients. Further, a high level of EPDR1 was shown to be correlated with advanced stage of HCC. Functional analysis revealed that EPDR1 is associated with multiple signaling pathways as well as pathways related to cancer and apoptosis. Notably, EPDR1 expression significantly correlated with purity and the infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Further, the EPDR1 expression significantly correlated with the expression of immune signatures, such as KIR2DL4, ITGAM, GATA3, STAT6, STAT5A, BCL6, STAT3, and HAVCR2.Conclusions: Our study identified EPDR1 as a novel prognostic biomarker in HCC. The expression of EPDR1 was shown to be associated with immune cell infiltration as well as the signature molecules that potentially regulate these processes during the carcinogenesis of HCC. With better understanding of its biological function, EPDR1 could become an effective target for HCC diagnosis and treatment in the future.

scholarly journals CYP4B1 is a prognostic biomarker and potential therapeutic target in lung adenocarcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247020
Author(s):  
Xiaoling Liu ◽  
Yichen Jia ◽  
Changyuan Shi ◽  
Dechen Kong ◽  
Yuanming Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Therapeutic Target ◽  
Prognostic Biomarker ◽  
Secondary Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Potential Therapeutic Target ◽  
Wide Range ◽  
Endogenous Compounds

CYP4B1 belongs to the mammalian CYP4 enzyme family and is predominantly expressed in the lungs of humans. It is responsible for the oxidative metabolism of a wide range of endogenous compounds and xenobiotics. In this study, using data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database, a secondary analysis was performed to explore the expression profile of CYP4B1, as well as its prognostic value in patients with lung adenocarcinoma (LUAD). Based on the obtained results, a significantly decreased CYP4B1 expression was discovered in patients with LUAD when compared with their normal counterparts (p<0.05), and was linked to age younger than 65 years (p = 0.0041), history of pharmaceutical (p = 0.0127) and radiation (p = 0.0340) therapy, mutations in KRAS/EGFR/ALK (p = 0.0239), and living status of dead (p = 0.0026). Survival analysis indicated that the low CYP4B1 expression was an independent prognostic indicator of shorter survival in terms of overall survival (OS) and recurrence-free survival (RFS) in patients with LUAD. The copy number alterations (CNAs) and sites of cg23440155 and cg23414387 hypermethylation might contribute to the decreased CYP4B1 expression. Gene set enrichment analysis (GSEA) suggested that CYP4B1 might act as an oncogene in LUAD by preventing biological metabolism pathways of exogenous and endogenous compounds and enhancing DNA replication and cell cycle activities. In conclusion, CYP4B1 expression may serve as a valuable independent prognostic biomarker and a potential therapeutic target in patients with LUAD.

scholarly journals High UBE2T mRNA expression and its prognostic significance in Ovarian cancer: a study based on data mining

2020 ◽  
Author(s):  
zenghong wu
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cell ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Rna Degradation ◽  
Gene Set Enrichment Analysis ◽  
Pathogenesis Related ◽  
Biologic Effect ◽  
The Difference

Abstract Objection Ovarian cancer (OC) affects approximately 22 000 women annually in the US and ranks 5th in cancer deaths, largely due to diagnosed with advanced stage1. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian cancer cases. Our study was to assess the prognostic meaningful of UBE2T expression in OC dependent on data acquired from TCGA and so as to increase further knowledge into the biological pathways involved in OC pathogenesis related to UBE2T.Method Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression.Results The scatter plot showed the difference of UBE2T expression between normal and tumor samples (P<0.01). In order to decide the biological interaction network of UBE2T in OC, we applied to tab Network in cBioPortal and the 50 most as often altered neighbor genes of UBE2T were showed utilizing Network and the most frequent alterations were HES1. The GSEA results showed that cell cycle, DNA replication, RNA degradation, some cancers, spliceosome, Huntington’s disease, oxidative phosphorylation are differentially enriched in UBE2T high expression phenotype. Cumulative survive showed that dendritic cell of immune infiltrates statistically significant (P<0.05) of UBE2T in OC indicating that dendritic cell significantly affecting the prognosis, it is worth further research and exploration.Conclusion Our study found that the expression of UBE2T was significantly increased in OC patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in OC, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.

scholarly journals Zic Family Member 2 (ZIC2): a Potential Diagnostic and Prognostic Biomarker for Pan-Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhengtong Lv ◽  
Lin Qi ◽  
Xiheng Hu ◽  
Miao Mo ◽  
Huichuan Jiang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Zinc Finger Protein ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Multiple Cancer ◽  
Survival Prognosis ◽  
Multiple Tumor ◽  
Immune Related Genes ◽  
Pan Cancer

Background: As a transcription factor, Zinc finger protein ZIC2 can interact with various DNAs and proteins. Current studies have shown that ZIC2 plays an oncogene role in various cancers. In this study, we systematically characterize the prevalence and predictive value of ZIC2 expression across multiple cancer types.Methods: We mined several public databases, including Oncomine, the Cancer Genome Atlas (TCGA), cBioPortal, Kaplan-Meier Plotter and PrognoScan to evaluated the differentially expressed ZIC2 between tumor samples and normal control samples in pan-cancner, and then explored the association between ZIC2 expression and patient survival, prognosis and clinicopathologic stage. We also analyzed the relationship between tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, tumor- and immune-related genes and ZIC2 expression. Finally, we explored the potential signaling pathway mechanism through gene set enrichment analysis (GSEA).Results: ZIC2 expression was higher in most cancer tissues compared with adjacent normal tissues. High ZIC2 expression was associated with worse prognosis and a higher clinicopathologic stage. ZIC2 expression was strongly associated with the TMB, MSI, tumor microenvironment and tumor- and immune-related genes. The GSEA revealed that multiple tumor- and immune-related pathways were differentially enriched in ZIC2 high or low expression phenotype.Conclusion: ZIC2 expression may be a potential prognostic molecular biomarker of poor survival in pan-cancer and may act as an oncogene with a strong effect in the processes of tumorigenesis and progression.

scholarly journals An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Roc Curves ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

scholarly journals A Starvation-Based 9-mRNA Signature Correlates With Prognosis in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Liver Cancer ◽  
Cancer Patients ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
Biological Processes ◽  
Gene Set Enrichment

BackgroundHepatocellular carcinoma (HCC) is one of the world’s most prevalent and lethal cancers. Notably, the microenvironment of tumor starvation is closely related to cancer malignancy. Our study constructed a signature of starvation-related genes to predict the prognosis of liver cancer patients.MethodsThe mRNA expression matrix and corresponding clinical information of HCC patients were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) was used to distinguish different genes in the hunger metabolism gene in liver cancer and adjacent tissues. Gene Set Enrichment Analysis (GSEA) was used to identify biological differences between high- and low-risk samples. Univariate and multivariate analyses were used to construct prognostic models for hunger-related genes. Kaplan-Meier (KM) and receiver-operating characteristic (ROC) were used to assess the model accuracy. The model and relevant clinical information were used to construct a nomogram, protein expression was detected by western blot (WB), and transwell assay was used to evaluate the invasive and metastatic ability of cells.ResultsFirst, we used univariate analysis to identify 35 prognostic genes, which were further demonstrated to be associated with starvation metabolism through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We then used multivariate analysis to build a model with nine genes. Finally, we divided the sample into low- and high-risk groups according to the median of the risk score. KM can be used to conclude that the prognosis of high- and low-risk samples is significantly different, and the prognosis of high-risk samples is worse. The prognostic accuracy of the 9-mRNA signature was also tested in the validation data set. GSEA was used to identify typical pathways and biological processes related to 9-mRNA, cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway, as well as biological processes related to the model. As evidenced by WB, EIF2S1 expression was increased after starvation. Overall, EIF2S1 plays an important role in the invasion and metastasis of liver cancer.ConclusionsThe 9-mRNA model can serve as an accurate signature to predict the prognosis of liver cancer patients. However, its mechanism of action warrants further investigation.

TRPV4 is a Prognostic Biomarker That Correlates With the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

2021 ◽  
Author(s):  
kai wang ◽  
Jun xing Feng ◽  
Zhi ling Zheng ◽  
Ying ze Chai ◽  
Hui jun Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transient Receptor Potential ◽  
Immune Cell ◽  
Colon Adenocarcinoma ◽  
Enrichment Analysis ◽  
Receptor Potential ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Free Interval ◽  
Pan Cancer

Abstract Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear.Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database.Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors.Conclusions: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples.

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