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Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis.

ABSTRACT: The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80-90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients' overall survival, which has great potential to serve as a clinical biomarker in KIRC.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6954481 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis.

Wang Qian Q Zhang Hao H Chen Quanbing Q Wan Zhenghua Z Gao Xiaoyong X Qian Wenhui W

Disease markers 20191230

The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80-90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAport ...[more]

PMID: 31976022

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Project description:Background Clear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer type with a high mortality rate. Due to a diverse range of biochemical alterations and a high level of tumor heterogeneity, it is crucial to select highly validated prognostic biomarkers to be able to identify subtypes of ccRCC early and apply precision medicine approaches. Methods Transcriptome data of ccRCC and clinical traits of patients were obtained from the GSE126964 dataset of Gene Expression Omnibus and The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) database. Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening were applied to detect common differentially co-expressed genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, survival analysis, prognostic model establishment, and gene set enrichment analysis were also performed. Immunohistochemical analysis results of the expression levels of prognostic genes were obtained from The Human Protein Atlas. Single-gene RNA sequencing data were obtained from the GSE131685 and GSE171306 datasets. Results In the present study, a total of 2,492 DEGs identified between ccRCC and healthy controls were filtered, revealing 1,300 upregulated genes and 1,192 downregulated genes. Using WGCNA, the turquoise module was identified to be closely associated with ccRCC. Hub genes were identified using the maximal clique centrality algorithm. After having intersected the hub genes and the DEGs in GSE126964 and TCGA-KIRC dataset, and after performing univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, ALDOB, EFHD1, and ESRRG were identified as significant prognostic factors in patients diagnosed with ccRCC. Single-gene RNA sequencing analysis revealed the expression profile of ALDOB, EFHD1, and ESRRG in different cell types of ccRCC. Conclusions The present results demonstrated that ALDOB, EFHD1, and ESRRG may act as potential targets for medical therapy and could serve as diagnostic biomarkers for ccRCC.

Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of kidney with high mortality. The pathogenesis of ccRCC is complicated and effective prognostic predictors for clinical practice are still limited. This study aimed to identify significant genes with prognostic influence in ccRCC via bioinformatics analysis.MethodsFour gene expression profiles were acquired from the Gene Expression Omnibus (GEO) database, including 168 ccRCC tissues and 143 normal tissues. Common differentially expressed genes (DEGs) between ccRCC tissues and normal kidney tissues were screened out. Then gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were investigated. Protein-protein interaction (PPI) network of the common DEGs was diagrammed and analyzed. Kaplan-Meier analysis was conducted to identify genes with prognostic influence in ccRCC. Gene Expression Profiling Interactive Analysis (GEPIA) was finally applied to validating differential expression of genes.ResultsNinety-nine common DEGs between ccRCC tissues and normal kidney tissues were eventually screened out (P<0.05, |log FC| >2). GO functional analysis showed that the down-regulated genes were enriched in excretion, negative regulation of cell proliferation, heparin binding and cellular response to BMP stimulus, etc. KEGG pathway analysis indicated that the common DEGs were particularly enriched in HIF-1 signaling pathway and aldosterone-regulated sodium reabsorption. Seven core DEGs were distinguished through PPI network analysis, of which 6 core genes ANGPTL4, CA9, CXCR4, LOX, EGF and HRG showed significantly prognostic difference in patients with ccRCC by Kaplan-Meier analysis (P<0.05). And GEPIA confirmed these genes were expressed differentially between tumor and normal tissues (P<0.05). High expression of HRG was correlated with good OS in ccRCC patients. Specifically, HRG was commonly down-regulated in ccRCC tissues compared with normal tissues according to GEPIA.ConclusionsOur study shows that high expression of HRG denotes a better prognosis in ccRCC patients. HRG is down-regulated in ccRCC tissues compared with normal kidney tissues. The selective expression pattern suggests that HRG could be a novel prognostic predictor and potential therapeutic target for ccRCC patients.

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Project description:ZDHHC-protein acyltransferases (ZDHHCs) are a family of 23 signature Asp-His-His-Cys (DHHC) domain-containing enzymes that mediate palmitoylation by covalent attachment of the 16-carbon fatty acid palmitate to thiol groups of specific cysteine residues in substrate proteins. Emerging evidence has shown abnormal expression of ZDHHCs in a variety of disease states, including cancer. Kidney renal clear cell carcinoma (KIRC) is the eighth most common type of cancer, which accounts for the majority of malignant kidney tumors. However, there are currently no effective therapeutic targets or biomarkers for clinical treatment and prognosis in KIRC. In this study, we first analyzed the expression pattern of the 23 ZDHHCs in KIRC using TCGA and GEPIA database, and found that the expression of ZDHHC2, 3, 6, 14, 15, 21, and 23 was significantly down-regulated whereas the expression of ZDHHC9, 17, 18, 19 and 20 was significantly up-regulated in KIRC patient tissues vs. normal tissues. And the expression of ZDHHC2, 3, 6, 9, 14, 15, and 21 in tumors decreased with the increase of the pathological stage of KIRC patients. Notably, KIRC patients with decreased expression of ZDHHC3, 6, 9, 14, 15, 17, 20, 21, 23 and increased expression of ZDHHC19 were significantly associated with poor prognosis. Further, we found that there was a significant correlation between ZDHHC3, 6, 9, 14, 15, 17, 19, 20, 21, 23 expressions and immune cell infiltration. Besides, high mRNA expression was the most common type of gene alteration and there was a high correlation among the expression of ZDHHC6, 17, 20 and 21. Finally, function prediction indicated that the immune or metabolic disorders or the activation of oncogenic signaling pathways caused by abnormal expression of these ZDHHCs may be important mechanisms of tumor progression and poor prognosis in patients with KIRC. Our results may provide novel insight for identifying tumor markers or molecular targets for the treatment of KIRC.

Dataset Information

Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis.

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Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis.

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