scholarly journals N6-Methyladenosine Writer Gene ZC3H13 Predicts Immune Phenotype and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Guo ◽  
Hongxiang Duan ◽  
Jinbo Chen ◽  
Jinhui Liu ◽  
Belaydi Othmane ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Cancer Specific Survival

BackgroundAlthough the RNA modification N6-methyladenosine ZC3H13 has been found to play vital regulatory roles in many types of cancers, its role in predicting the tumor immune microenvironment (TME) and response to immune checkpoint blockade (ICB) in kidney renal clear cell carcinoma (KIRC) remains unclear.MethodsWe comprehensively analyzed the expression, prognostic significance and immunological role of ZC3H13 in pan-cancers and systematically correlated ZC3H13 with TME cell-infiltration, ICB response and targeted therapy in KIRC. The data were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Broad Institute Cancer Cell Line Encyclopedia (CCLE) and DrugBank database. Also, we performed RNA sequencing (RNA-seq) of 46 renal cell carcinoma tissues and 11 adjacent normal tissues to validate our result. All analyses were implemented using R software, version 3.6.3.ResultsZC3H13 was significantly differentially expressed in most tumors. However, its expression profiles and prognostic significance were consistent only in KIRC, regardless of overall survival, progression-free survival and cancer-specific survival. Additionally, ZC3H13 expression was correlated with clinicopathological factors in KIRC. Furthermore, we found that ZC3H13 might shape a noninflamed phenotype and could predict a lower response to ICB in KIRC. These results could be validated in our own RNA-seq data. Tumor mutation burden (TMB) was significantly higher in the low ZC3H13 group. Finally, we found that ZC3H13 could predict the sensitivity of targeted therapy for KIRC.ConclusionsZC3H13 might shape a noninflamed phenotype in KIRC. Moreover, ZC3H13 could predict the prognosis and clinical response of ICB and the sensitivity to targeted therapies in KIRC.

scholarly journals Identification of Tumor Microenvironment-Related Genes in Kidney Renal Clear Cell Carcinoma Patients via Bioinformatic Analysis

2021 ◽  
Author(s):  
Rongjiong Zheng ◽  
Yaosen SHao ◽  
Mingming Wang ◽  
Yeli Tang ◽  
Meiling Hu
Keyword(s):  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment

Abstract BackgroundTumor microenvironment has been implicated in the development and progression of cancers. However, the prognostic significance of tumor microenvironment-related genes in kidney renal clear cell carcinoma (KIRC) remains unclear. MethodsIn this study, we obtained and analyzed gene expression profiles from The Cancer Genome Atlas database. Stromal and immune scores were calculated based on the ESTIMATE algorithm. ResultsIn the discovery series of 537 patients, we identified a list of differentially expressed genes which was significantly associated with prognosis in KIRC patients. Protein-protein interaction networks and functional enrichment analysis were both performed, indicating that these identified genes were related to the immune response. ConclusionsThe tumor microenvironment-related genes could serve as the potential biomarkers for KIRC.

scholarly journals Identification of Potential Biomarkers For The Prognosis, Diagnosis, And Targeted Therapy in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Fang Cheng ◽  
Qiang Li ◽  
Jinglin Wang ◽  
Yumei Wang ◽  
Zhendi Wang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Reduction Process ◽  
Renal Clear Cell Carcinoma ◽  
Biological Functions ◽  
Hub Genes

Abstract Background: Kidney renal clear cell carcinoma (KIRC) is the most common renal cell carcinoma types. This work aims to find potential diagnostic biomarkers and explore the biological functions related to the prognosis of KIRC. Method: First, Gene expression profiles of GSE15641, GSE72304, GSE71963, GSE53757, and GSE36895 from GEO database. Differentially expressed genes (DEGs) were identified by the limma package in R software. Next, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed. Then protein-protein interaction (PPI) and hub genes were visualized by Cytoscape with STRING database. Then, we evaluate the predictive potential of hub genes expressions in KIRC with TCGA data. In addition, the relevant biological functions were identified using GSEA. Finally, we examined the differences of hub genes expression between multiple tumor tissues and normal tissues.Results: A total of 141 DEGs (including 99 upregulated and 42 downregulated genes) were identified. GO analysis indicated that DEGs were mainly involved in oxidation-reduction process and response to hypoxia. The KEGG analysis primarily related to PPAR signaling pathway, and HIF-1 signaling pathway. Moreover, the PPI analysis revealed 5 hub genes (AOX1, ALDH6A1, ABAT, HADH, and PCCA). The 5 hub genes were significantly correlated with KIRC progression and might have prognostic significance for KIPC patients. And low expression of the hub genes associated biological pathways were enriched in the NF-KB activation, focal adhesion, and JAK-STAT signaling pathway, respectively. Conclusion: Our study demonstrated that AOX1, ALDH6A1, ABAT, HADH, and PCCA can be used as prognostic biomarkers for KIRC.

GALNT14 expression in renal clear cell carcinoma and its effect on prognosis

2021 ◽  
Author(s):  
Yuqin Wei ◽  
Fan Wu ◽  
Shengfeng Zhang ◽  
Yanlin Tan ◽  
Qunying Wu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Regulatory Pathways ◽  
Cox Analysis ◽  
The Relationship

Abstract Background The expression of GALNT14 in kidney renal clear cell carcinoma (KIRC) and its clinical significance remains unknown. Methods The KIRC data expressed by GALNT14 was downloaded from The Cancer Genome Atlas (TCGA) database. The expression of GALNT14 was analyzed by R software, Perl software and online analysis database. The relationship between GALNT14 expression and clinicopathological features in KIRC was analyzed by univariate, multivariate Cox regression and some databases. Gene Expression Profling Interactive Analysis (GEPIA), Starbase v3.0, UALCAN, and Kaplan-Meier were used to analyze the relationship between GALNT14 expression and overall survival (OS) in KIRC. UALCAN detects the expression of GALNT14 methylation in KIRC. Linkedomics and Genemania were used to analyze the gene co-expression of GALNT14. Gene Set Enrichment Analysis (GSEA) was performed to search for potential regulatory pathways. Results We found that GALNT14 was overexpressed in KIRC (p=1.433e-25). Patients with high GALNT14 expression in KIRC had a better prognosis than patients with low GALNT14 expression (p=0.008). In addition, high GALNT14 expression in KIRC was significantly associated with low T stage and positive OS (p<0.05). Univariate Cox analysis showed that GALNT14 was positively correlated with OS (p<0.001). Multivariate Cox analysis showed that GALNT14 was associated with OS (p<0.001), age (p=0.01) and histological grade (p=0.02). GALNT14 methylation is low expressed in KIRC (p<0.001). GSEA analysis showed that GALNT14 was enriched in histidine metabolism, peroxisome, and renin-angiotensin system pathways. Conclusion GALNT14 can be used as an independent prognostic factor for renal clear cell carcinoma and a potential target for clinical diagnosis and treatment of KIRC.

scholarly journals Comprehensive Analysis of the Immune Infiltrates of Pyroptosis in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuolun Sun ◽  
Changying Jing ◽  
Xudong Guo ◽  
Mingxiao Zhang ◽  
Feng Kong ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Carcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Risk Model ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Risk Scores

Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.

scholarly journals LY96 Upregulation Promotes Kidney Renal Clear Cell Carcinoma (KIRC)

2021 ◽  
Author(s):  
Ji-li Xu ◽  
Yong Guo
Keyword(s):  
Transcription Factors ◽  
Cell Carcinoma ◽  
Dna Methyltransferase ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Related Factors ◽  
Beneficial Effects ◽  
Highly Correlated

Abstract Background: LY96 has been reported to be relevant with kidney inflammatory injury but the function of this gene in kidney renal clear cell carcinoma (KIRC) remains unknown.Methods: Various online tools were applied to analyze the roles of LY96 in KIRC using data from the Cancer Genome Atlas. Differential LY96 expression and overall survival (OS) based on different expression levels were analyzed through Oncomine and GEPIA tools. The alterations, related genes, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways of LY96 were explored via cBioPortal and STRING database. LinkedOmics and Cistrome DB Toolkit were utilized to identify targets of kinase, miRNAs, and transcription factors. The relationship between LY96 and some associated genes or regulatory factors was displayed via GeneMANIA and TIMER tool. TISIDB revealed correlations between LY96 expression and immune-associated factors in the tumor microenvironment. Results: High LY96 expression level was observed in KIRC and associated with poor prognosis and diverse clinical characteristics. LY96 often amplified in KIRC and was mostly linked to the inflammatory response. Several highly correlated genes, kinase targets, transcription factors, and DNA methyltransferase that may interact with LY96 were all identified. Our study also demonstrated that various immune-related factors were relevant to LY96 in KIRC. Conclusions: Our study has shown the complex relationships between LY96 and KIRC from diverse angles. High LY96 expression had an adverse effect on the prognosis of KIRC. To find effective demethylation agents and transcription factors inhibitors targeting LY96 may have beneficial effects on the survival of KIRC patients.

OSkirc: a web tool for identifying prognostic biomarkers in kidney renal clear cell carcinoma

2019 ◽  
Vol 15 (27) ◽  
pp. 3103-3110 ◽  
Author(s):  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Linna Ge ◽  
Xiaoxiao Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Web Application ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
P Value ◽  
Survival Plot

Aim: To develop a free and quick analysis online tool that allows users to easily investigate the prognostic potencies of interesting genes in kidney renal clear cell carcinoma (KIRC). Patients & methods: A total of 629 KIRC cases with gene expression profiling data and clinical follow-up information are collected from public Gene Expression Omnibus and The Cancer Genome Atlas databases. Results: One web application called Online consensus Survival analysis for KIRC (OSkirc) that can be used for exploring the prognostic implications of interesting genes in KIRC was constructed. By OSkirc, users could simply input the gene symbol to receive the Kaplan–Meier survival plot with hazard ratio and log-rank p-value. Conclusion: OSkirc is extremely valuable for basic and translational researchers to screen and validate the prognostic potencies of genes for KIRC, publicly accessible at http://bioinfo.henu.edu.cn/KIRC/KIRCList.jsp

scholarly journals Abnormal Expression and Prognostic Significance of EPB41L1 in Kidney Renal Clear Cell Carcinoma Based on Data Mining

2020 ◽  
Author(s):  
Taotao Liang ◽  
Siyao Sang ◽  
Qi Shao ◽  
Zhichao Deng ◽  
Ting Wang ◽  
...  
Keyword(s):  
Data Mining ◽  
Cell Adhesion ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma

Abstract Background: EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remains to be investigated.Methods: In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC were analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them were visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.Results: The results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 was associated with cell adhesion. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion.Conclusions: In summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.

scholarly journals Expression and prognostic significance of Src family members in renal clear cell carcinoma

2012 ◽  
Vol 107 (5) ◽  
pp. 856-863 ◽  
Author(s):  
T Qayyum ◽  
P A McArdle ◽  
G W Lamb ◽  
F Jordan ◽  
C Orange ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Prognostic Significance ◽  
Family Members ◽  
Renal Clear Cell Carcinoma

scholarly journals NFIB promotes the migration and progression of kidney renal clear cell carcinoma by regulating PINK1 transcription

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10848
Author(s):  
Ninghua Wang ◽  
Jing Yuan ◽  
Fei Liu ◽  
Jun Wei ◽  
Yu Liu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Transcriptional Level ◽  
Nuclear Factor I ◽  
Cancer Genome Atlas ◽  
Metastasis Rate

Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive type of renal cell carcinoma. Due to high mortality rate, high metastasis rate and chemical resistance, the prognosis of KIRC patients is poor. Therefore, it is necessary to study the mechanisms of KIRC development and to develop more effective prognostic molecular biomarkers to help clinical patients. In our study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to investigate that the expression of nuclear factor I B (NFIB) is significantly higher in KIRC than in adjacent tissues. Moreover, NFIB expression levels are associated with multiple clinical pathological parameters of KIRC, and KIRC patients with high NFIB expression have poor prognosis, suggesting that NFIB may play vital roles in the malignant development of KIRC. Further studies demonstrated that NFIB could promote the progression and metastasis of KIRC and participate in the regulation of PTEN induced kinase 1 (PINK1). Furthermore, we used chromatin immunoprecipitation (ChIP) experiments to confirm that NFIB binds to the PINK1 promoter and regulates its expression at the transcriptional level. Further experiments also confirmed the important roles of PINK1 in promoting the development of tumors by NFIB. Hence, our data provide a new NFIB-mediated regulatory mechanism for the tumor progression of KIRC and suggest that NFIB can be applied as a new predictor and therapeutic target for KIRC.

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