scholarly journals Identification and validation of HSD11B2 as a biomarker for metastasis and prognosis of clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Shiqi Miao ◽  
Jing Song ◽  
Teng Wang ◽  
Qingmao Rao ◽  
Yongyao Tang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Extracellular Matrix ◽  
Survival Analysis ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Enrichment Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Qrt Pcr

Abstract Background : Metastasis of clear cell renal cell carcinoma (ccRCC) is an important cause of death. The purpose of this study was to study the key gene in the process of tumor metastasis of ccRCC. Methods : Expression profiles of metastatic ccRCC and primary ccRCC were downloaded from the GEO database. Expression profiling and clinical data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) dataset. The R limma package was used to identify differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for overlapping DEGs. Verification of mRNA expression and survival analysis in the GEPIA2 database further identified the key gene. The expression of the key gene in clinical specimens was detected by quantitative real-time PCR (qRT-PCR). Univariate and multivariate cox analysis were performed to determine whether the key gene was independent prognostic factor. Gene Set Enrichment Analysis (GSEA) was used to identify HSD11B2 related signaling pathways. The correlations between the key gene and tumor immune infiltrates were investigated via TISIDB database. Results ：A total of 20 DEGs were screened from GSE22541, GSE85258, and GSE105261 datasets. Enrichment analysis indicated that the DEGs were mainly enriched in the extracellular matrix organization, collagen-containing extracellular matrix, extracellular matrix structural constituent, and protein digestion and absorption. Verification of mRN expression and survival analysis identified the key gene HSD11B2. qRT-PCR results showed A that HSD11B2 level was significantly down-regulated in ccRCC tissues compared with adjacent normal tissues. Multivariate Cox regression analysis showed that HSD11B2 expression was an independent prognostic factor for ccRCC patients. GSEA enrichment results showed that low expression of HSD11B2 could enrich cancer signaling pathways such as Nod-like receptor signaling pathway, cytoplasmic DNA sensing pathway and P53 signaling pathway. Immune analysis showed a significant correlation between HSD11B2 and tumor immune infiltrates in ccRCC. Conclusions : These findings suggest that HSD11B2 may play a key role in the metastasis of ccRCC, and HSD11B2 is correlated with prognosis and tumor immune infiltrates.

scholarly journals 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

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.

scholarly journals Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

2017 ◽  
Vol 8 (4) ◽  
pp. 665-673 ◽  
Author(s):  
Qiao Zhang ◽  
Xiaojia Yi ◽  
Zhe Yang ◽  
Qiaoqiao Han ◽  
Xuesong Di ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Potential Prognostic Factor

scholarly journals Development and Interpretation of a Genomic Instability Derived lncRNAs Based Risk Signature as a Predictor of Prognosis for Clear Cell Renal Cell Carcinoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiying Yang ◽  
Xiaoling Xiong ◽  
Hua Li
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Genomic Instability ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Prognosis Prediction

BackgroundClear cell renal cell carcinoma (ccRCC) is a kind of frequently diagnosed cancer, leading to high death rate in patients. Genomic instability (GI) is regarded as playing indispensable roles in tumorigenesis and impacting the prognosis of patients. The aberrant regulation of long non-coding RNAs (lncRNAs) is a main cause of GI. We combined the somatic mutation profiles and expression profiles to identify GI derived lncRNAs (GID-lncRNAs) in ccRCC and developed a GID-lncRNAs based risk signature for prognosis prediction and medication guidance.MethodsWe decided cases with top 25% cumulative number of somatic mutations as genomically unstable (GU) group and last 25% as genomically stable (GS) group, and identified differentially expressed lncRNAs (GID-lncRNAs) between two groups. Then we developed the risk signature with all overall survival related GID-lncRNAs with least absolute shrinkage and selection operator (LASSO) Cox regression. The functions of the GID-lncRNAs were partly interpreted by enrichment analysis. We finally validated the effectiveness of the risk signature in prognosis prediction and medication guidance.ResultsWe developed a seven-lncRNAs (LINC00460, AL139351.1, AC156455.1, AL035446.1, LINC02471, AC022509.2, and LINC01606) risk signature and divided all samples into high-risk and low-risk groups. Patients in high-risk group were in more severe clinicopathologic status (higher tumor grade, pathological stage, T stage, and more metastasis) and were deemed to have less survival time and lower survival rate. The efficacy of prognosis prediction was validated by receiver operating characteristic analysis. Enrichment analysis revealed that the lncRNAs in the risk signature mainly participate in regulation of cell cycle, DNA replication, material metabolism, and other vital biological processes in the tumorigenesis of ccRCC. Moreover, the risk signature could help assess the possibility of response to precise treatments.ConclusionOur study combined the somatic mutation profiles and the expression profiles of ccRCC for the first time and developed a GID-lncRNAs based risk signature for prognosis predicting and therapeutic scheme deciding. We validated the efficacy of the risk signature and partly interpreted the roles of the seven lncRNAs composing the risk signature in ccRCC. Our study provides novel insights into the roles of genomic instability derived lncRNAs in ccRCC.

Systematic Analyses of The Role of Prognostic And Immunological of EIF3A, A Reader Protein, In Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Yi Zhang ◽  
Xiaoliang Hua ◽  
Haoqiang Shi ◽  
Li Zhang ◽  
HaiBing Xiao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Immune Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Multivariate Analyses ◽  
Enrichment Analysis ◽  
Marker Genes ◽  
Cell Renal Cell Carcinoma

Abstract Background: Eukaryotic initiation factor 3a, EIF3A, as a “reader” protein for RNA methylation, has been found to be related to promote tumorigenesis in different variety of cancers. The impaction of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be expounded. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between expression and immune infiltration.Methods: We collected 29 m6a related mRNA data and clinicopathological parameters from Cancer Genmoe Atlas (TCGA) database. Logistic regression analyses were used to analyze the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) were applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize forcefully independent factor in associated with overall survival (OS) and diseases free survival (DFS). Nomogram was aim at predicting the 1-, 3-and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to the potential function and related signaling pathways of EIF3A expression. To investigate EIF3A of co-expressed genes, we used LinkedOmics and its result was undertaken enrichment analysis. Simultaneously, to employ LinkedOmics and STRING dataset drew a conclusion that EIF3A co-expressed genes and visualized via Cytoscape. Finally, we evaluated that EIF3A expression correlated between with infiltration of immune cells and the expression of marker genes in ccRCC by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA).Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was connected with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with poor prognosis. The result of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that high expression was enriched in renal cell carcinoma pathway and so on. EIF3A expression was significantly positively correlated with B cells, CD8+T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most of marker genes of immune cells.Conclusions: EIF3A could serve as potential biomarkers for prognostic and diagnostic stratification factor for ccRCC and is related with immune cells infiltrates.

scholarly journals PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma

Aging ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 7585-7602 ◽  
Author(s):  
Giuseppe Stefano Netti ◽  
Giuseppe Lucarelli ◽  
Federica Spadaccino ◽  
Giuseppe Castellano ◽  
Margherita Gigante ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Prognostic Value of The Ratio of Maximum To Minimum Diameter of Primary Tumor In Metastatic Clear Cell Renal Cell Carcinoma

2022 ◽  
Author(s):  
Hongzhe Shi ◽  
Chuanzhen Cao ◽  
Li Wen ◽  
Lianyu Zhang ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Primary Tumor ◽  
Renal Cell ◽  
Prognostic Value ◽  
Tumor Necrosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Abstract Background: Several models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC).Methods: Patients with mccRCC (n=213) treated with sunitinib from January 2008 to December 2018 were identified. Cut-off value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan-Meier method.Results: The optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD≥1.34 group had shorter PFS (9.6 versus 17.7 months, p<0.001) and OS (25.5 versus 32.6 months, p<0.001) than patients in ROD<1.34 group. After adjustment for other factors, multivariate analysis showed ROD≥1.34 was an independent prognostic factor for PFS (p<0.001) and OS (p=0.006). Patients in ROD³1.34 group presented higher proportions of T3/4 stage (92.9% versus 7.1%, p=0.012), WHO/ISUP grade III/IV (72.0% versus 28.0%, p=0.010), tumor necrosis (71.0% versus 29.0%, p=0.039), sarcomatoid differentiation (79.1% versus 20.9%, p=0.007), poor MSKCC risk score (78.4% versus 21.6%, p<0.001) and poor IMDC risk score (74.4% versus 25.6%, p<0.001) than ROD<1.34 group.Conclusion: Primary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high T stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score.

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