Three novel hub genes and their clinical significance in clear cell renal cell carcinoma

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

Download Full-text

Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01889-8 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Wuping Yang ◽

Kenan Zhang ◽

Lei Li ◽

Yawei Xu ◽

Kaifang Ma ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Clinical Significance ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Cell Renal Cell Carcinoma ◽

Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

Download Full-text

Identification of prognostic related hub genes in clear-cell renal cell carcinoma via bioinformatical analysis

Chinese Medical Sciences Journal ◽

10.24920/003651 ◽

2019 ◽

Vol 0 (0) ◽

pp. 1

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Hub Genes ◽

Cell Renal Cell Carcinoma ◽

Bioinformatical Analysis

Download Full-text

The expression and clinical significance of matrix metalloproteinase 7 and tissue inhibitor of matrix metalloproteinases 2 in clear cell renal cell carcinoma

Experimental and Therapeutic Medicine ◽

10.3892/etm.2012.859 ◽

2012 ◽

Vol 5 (3) ◽

pp. 890-896 ◽

Cited By ~ 14

Author(s):

HONGSHENG LU ◽

ZHAOHUI YANG ◽

HUI ZHANG ◽

MEIFU GAN ◽

TAO ZHOU ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Matrix Metalloproteinases ◽

Matrix Metalloproteinase ◽

Cell Carcinoma ◽

Clinical Significance ◽

Renal Cell ◽

Clear Cell ◽

Tissue Inhibitor ◽

Cell Renal Cell Carcinoma ◽

Matrix Metalloproteinase 7

Download Full-text

Differential expression and clinical significance of serum protein among patients with clear-cell renal cell carcinoma

Cancer Biomarkers ◽

10.3233/cbm-150490 ◽

2015 ◽

Vol 15 (4) ◽

pp. 485-491 ◽

Cited By ~ 6

Author(s):

Yiliyaer Nuerrula ◽

Mulati Rexiati ◽

Qiang Liu ◽

Yu-Jie Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Differential Expression ◽

Clinical Significance ◽

Serum Protein ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

Download Full-text

Functional Assessment of Four Novel Immune-Related Biomarkers in the Pathogenesis of Clear Cell Renal Cell Carcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.621618 ◽

2021 ◽

Vol 9 ◽

Author(s):

Daojun Lv ◽

Xiangkun Wu ◽

Ming Wang ◽

Wenzhe Chen ◽

Shuxin Yang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Rank Aggregation ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Hub Genes ◽

Cell Renal Cell Carcinoma ◽

Network Analyses

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma whose pathogenesis is not well understood. We aimed at identifying novel immune-related biomarkers that could be valuable in the diagnosis and prognosis of ccRCC.MethodsThe Robust Rank Aggregation (RRA) method was used to integrate differently expressed genes (DEGs) of 7 Gene Expression Omnibus (GEO) datasets and obtain robust DEGs. Weighted gene co-expression network analyses (WGCNA) were performed to identify hub genes associated with clinical traits in The Cancer Genome Atlas (TCGA) database. Comprehensive bioinformatic analyses were used to explore the role of hub genes in ccRCC.ResultsFour hub genes IFI16, LMNB1, RHBDF2 and TACC3 were screened by the RRA method and WGCNA. These genes were found to be up-regulated in ccRCC, an upregulation that could be due to their associations with late TNM stages and tumor grades. The Receiver Operating Characteristic (ROC) curve and Kaplan-Meier survival analysis showed that the four hub genes had great diagnostic and prognostic values for ccRCC, while Gene Set Enrichment Analysis (GSEA) showed that they were involved in immune signaling pathways. They were also found to be closely associated with multiple tumor-infiltrating lymphocytes and critical immune checkpoint expressions. The results of Quantitative Real-time PCR (qRT-PCR) and immunohistochemical staining (IHC) analysis were consistent with bioinformatics analysis results.ConclusionThe four hub genes were shown to have great diagnostic and prognostic values and played key roles in the tumor microenvironment of ccRCC.

Download Full-text

Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

BioMed Research International ◽

10.1155/2020/2137319 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Dengyong Xu ◽

Yuzi Xu ◽

Yiming Lv ◽

Fei Wu ◽

Yunlong Liu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Early Diagnosis ◽

Cell Carcinoma ◽

Renal Cell ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Clear Cell ◽

Clinical Stage ◽

Hub Genes ◽

Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information—normal tissue and ccRCC stages I, II, III, and IV—and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.

Download Full-text