scholarly journals Identification of the Role of GLS2 in the Development and Progression of Clear Cell Renal Cell Carcinoma.

2020 ◽  
Author(s):  
dantong sun ◽  
lu tian ◽  
yang wo ◽  
han zhao ◽  
weihua yan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clear Cell ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Tissues ◽  
Basic Characteristics ◽  
Geo Database

Abstract Background The incidence of RCC has drastically increased in recent years. The large intratumor heterogeneity of RCC, especially ccRCC, usually leads to treatment failure. In addition, single biomarkers have a limited ability to predict prognosis. Therefore, we performed this study to select variables and provided a simple but efficient way to predict prognosis.MethodThree studies from GEO database were involved in the DEGs selection. A total of 840 RCC patients and 524 ccRCC patients from TCGA database were involved in the prognostic analyses. Nomograms based on Cox regression model were used to select variables to predict the prognosis, and GSEA was used to demonstrate the potential pathways altered by gene expression.ResultOur study suggested that DEGs existed between metastatic and primary tumor tissues. Loss of GLS2 was related to poor prognosis in RCC and ccRCC. These results revealed that GLS2 expression, combined with basic characteristics, including age and TNM stage, could efficiently predict prognosis. GLS2 serves as a tumor suppressor in ccRCC, loss of GLS2 function endows cells with oncogenic functions and is related to advanced disease. According to the GSEA results, loss of GLS2 function may alter the cell cycle by activating the E2F pathway.ConclusionGLS2 is a tumor suppressor in RCC. Loss of GLS2 function in ccRCC predicts a poor prognosis via the underlying E2F pathway. Nomograms based on DEGs and clinical features provide physicians with a simple but efficient way to predict prognosis. Further studies are needed to verify the pathway in our study.

scholarly journals Loss of GLS2 function is essential for obtaining oncogenic functions and promotes the progression of clear cell renal cell carcinoma.

2020 ◽  
Author(s):  
dantong sun ◽  
Lu Tian ◽  
Han Zhao ◽  
Weihua Yan ◽  
Xiaojuan Wei ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clear Cell ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Tissues ◽  
Basic Characteristics ◽  
Selection Of ◽  
Geo Database

Abstract Background The incidence of RCC has drastically increased in recent years. The large intratumor heterogeneity of RCC, especially ccRCC, usually leads to treatment failure. In addition, single biomarkers have a limited ability to predict prognosis. Therefore, we performed this study to select variables and provided a simple but efficient way to predict prognosis. Method Three studies from the GEO database were involved in the selection of DEGs. A total of 840 RCC patients and 524 ccRCC patients from the TCGA database were involved in the prognostic analyses. Nomograms based on the Cox regression model were used to select variables to predict the prognosis, and GSEA was used to demonstrate the potential pathways altered by gene expression. Result Our study suggested that DEGs existed between metastatic and primary tumor tissues. Loss of GLS2 function was related to poor prognosis in RCC and ccRCC. These results revealed that GLS2 expression combined with basic characteristics, including age and TNM stage, could efficiently predict prognosis. GLS2 serves as a tumor suppressor in ccRCC, and loss of GLS2 function endows cells with oncogenic functions and is related to advanced disease. According to the GSEA results, loss of GLS2 function may alter the cell cycle by activating the E2F pathway. Conclusion GLS2 is a tumor suppressor in RCC. Loss of GLS2 function in ccRCC predicts a poor prognosis via the E2F pathway. Nomograms based on DEGs and clinical features provide doctors with a simple but efficient way to predict prognosis. Further studies are needed to verify the pathway in our study.

scholarly journals G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression

2020 ◽  
Author(s):  
Zhe Yang ◽  
Qiao Zhang ◽  
Yueli Ni ◽  
Qiaoqiao Han ◽  
Shujie Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cyclin E1 ◽  
Mmp9 Expression

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin E1 and MMP9 in G6PD-mediated ccRCC progression. Methods: Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin E1 and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin E1 and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin E1 and MMP9 expression were investigated by using a series of cytological function assays in vitro. To verify this mechanism in vivo, xenografted mice models were established. Results: G6PD, Cyclin E1 and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration in vitro, and enhanced ccRCC development in vivo, more likely through enhancing Cyclin E1 and MMP9 expression. Conclusion: These findings present G6PD, Cyclin E1 and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.

Pathological significance of C3aR signaling in the tumor cells of clear cell renal cell carcinoma: a clinical observation

2020 ◽  
Author(s):  
Jing-Min Zheng ◽  
Xiong Tian ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Tumor Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Ki 67 ◽  
Tumor Tissues

Abstract Background Increasing evidences suggest that anaphylotoxin-induced signaling is involved in tumor pathogenesis, but the exact role of C3a/C3aR signaling in clear cell renal cell carcinoma (ccRCC) still remains to be investigated. The aim of the study was to investigate the pathological significance of C3a/C3aR signaling in ccRCC. Methods The expression of C3aR and C3 mRNA in the tumor tissues of ccRCC patients were analyzed by using the data from TCGA database. The expression of C3aR and C3c protein in the tumor tissues of another 129 ccRCC patients were examined by immunohistochemistry. Results Compared with the normal controls, both C3aR and C3 mRNA increased in the tumor tissues. Patients with higher C3 mRNA had shorter survival time. Immunostaining for C3aR and C3c also increased in the tumor tissues when compared with the adjacent normal renal tissues. Higher level of C3aR in the tumor cells and C3c in the tumor tissues were found to be associated with indices reflecting poor prognosis including higher tumor grade, the presence of necrosis in tumor tissues and shorter survival time. Besides, the level of C3aR in the tumor cells and C3c in the tumor tissues were found to correlate with the level of Vimentin, E-Cadherin and the ratio of Ki-67 positive tumor cells. Conclusions These results support the idea that C3aR signaling is over-activated in the tumor cells and may contribute to the progression of ccRCC. Inducing EMT and promoting the proliferation of tumor cells might be among the mechanisms underlying the role of C3aR signaling in ccRCC.

scholarly journals Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiu Zhengqi ◽  
Guo Zezhi ◽  
Jiang Lei ◽  
Qiu He ◽  
Pan Jinyao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
Clear Cell ◽  
Regression Analyses ◽  
Prognostic Role ◽  
Pyruvate Metabolism ◽  
Cell Renal Cell Carcinoma ◽  
Pathologic Features

AbstractThis study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene–gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e−19). Kaplan–Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e−05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e−05), and high level of stage_T (T3-4, p = 4.373e−05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin–angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.

scholarly journals Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma

Neoplasia ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. 339-346 ◽  
Author(s):  
Jun Li ◽  
Joost Kluiver ◽  
Jan Osinga ◽  
Helga Westers ◽  
Maaike B van Werkhoven ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Epithelial Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tubular Epithelial Cells ◽  
Cell Renal Cell Carcinoma ◽  
Functional Studies

scholarly journals m6A modification patterns and tumor immune landscape in clear cell renal carcinoma

2021 ◽  
Vol 9 (2) ◽  
pp. e001646
Author(s):  
Jiehui Zhong ◽  
Zezhen Liu ◽  
Chao Cai ◽  
Xiaolu Duan ◽  
Tuo Deng ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Clear Cell ◽  
Comprehensive Evaluation ◽  
Principal Component ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Specific Tumor ◽  
Cell Renal Carcinoma

BackgroundRecent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive.MethodsWe comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore.ResultsWe identified three m6Aclusters—characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC.ConclusionsThis study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.

scholarly journals Bim Expression in Peritumoral Lymphocytes is Associated with Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma

Kidney Cancer ◽  
2021 ◽  
pp. 1-7
Author(s):  
Bimal Bhindi ◽  
Elizabeth Bearrick ◽  
John C. Cheville ◽  
Christine M. Lohse ◽  
Ross J. Mason ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Immunohistochemistry Staining ◽  
Multivariable Adjustment

Background: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. Objective: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). Methods: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. Results: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95%CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95%CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS (p = 0.68) or OS (p = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. Conclusion: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients.

scholarly journals Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

2021 ◽  
Author(s):  
Qingqing Zhou ◽  
Jiajun Li ◽  
Chao Ge ◽  
Jinsi Chen ◽  
Wei Tian ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Background: Aberrant expression of SNX5 can contribute to tumourigenesis, invasion, and metastasis of several human cancers. However, the clinicopathological and biological significance of SNX5 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of this study was to examine the role of SNX5 in the progression of ccRCC.Methods: Immunohistochemical (IHC), Western blot, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to detect the expression of indicated molecules. The biological role of SNX5 in ccRCC cells was evaluated by CCK8, colony formation, transwell assay, subcutaneous tumor formation as well as veil tail injection. ChIP assay and luciferase reporter assay were used to determine the direct binding of KLF9 to the promoter of the SNX5 gene.Results: SNX5 expression was downregulated in human ccRCC tissues. SNX5 expression was negatively correlated with tumor size, AJCC stage, tumor thrombus of inferior vena cava (IVC) and poor prognosis of ccRCC. Ectopic expression of SNX5 inhibited ccRCC cell proliferation and metastasis whereas knockdown of SNX5 increase these activities both in vitro and in vivo. Mechanistically, overexpression of SNX5 blocked internalization and intracellular trafficking of CD44 in ccRCC cells. Exogenous expression of CD44 partially rescued the inhibitory effects of SNX5 on the proliferation and invasion activity of ccRCC cells. Knockdown of SNX5 in ccRCC cells was associated with epithelial mesenchymal transition (EMT), including the down-regulation of E-cadherin, ZO-1 and Claudin-1 and the concomitant up-regulation of Snail and N-cadherin. In addition, SNX5 inhibited TGF-β-induced migration, invasion and EMT in ccRCC cells. Moreover, we observed a significant correlation between SNX5 expression and E-cadherin levels in ccRCC patients. In addition, KLF9 directly bound to the SNX5 promoter and increased SNX5 transcription. SNX5 expression was closely correlated with KLF9 expression in ccRCC. Moreover, we found that the combination of SNX5 and CD44 or E-cadherin or KLF9 was a more powerful predictor of poor prognosis than either parameter alone.Conclusion: Collectively, our data reveal a mechanism that KLF9-mediated SNX5 expression was associated with poor prognosis via trafficking of CD44 and promoting EMT in ccRCC. SNX5 may be a potential prognostic biomarker and therapeutic target for patients with ccRCC.

scholarly journals Pseudogene HSPA7 is a Poor Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and Correlated With Immune Infiltrates

2021 ◽  
Author(s):  
Chunjin Ding ◽  
Rundong He ◽  
Jinghan Zhang ◽  
Zhan Dong ◽  
Jun Wu
Keyword(s):  
Cox Regression ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Renal Clear Cell Carcinoma ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Infiltrating Cells ◽  
Cox Analysis

Abstract Background: Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer. Methods: Firstly,we used Logistic regression,the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the level of HSPA7 expressed in KIRC,then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival(OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC. Results: The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRCpatints.GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell.Conclusions: Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.

scholarly journals RNF43 is a Novel Tumor Suppressor and Prognostic Indicator in Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Dawei Zhu ◽  
Lei Zhang ◽  
Xiaokai Shi ◽  
Shenglin Gao ◽  
Chuang Yue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Prognostic Indicator ◽  
Cell Renal Cell Carcinoma ◽  
Targeted Drug

Identifying prognostic indicators of clear cell renal cell carcinoma (ccRCC) and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis. This study investigated the clinical significance and biological role of Ring finger protein 43 ( RNF43) in ccRCC. Two independent cohorts of patients with ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical analyses. In vitro and in vivo experiments, RNA-seq, and other techniques were used to determine the biological role of RNF43 in ccRCC and related molecular mechanisms. RNF43 expression was commonly decreased in ccRCC specimens, and low expression of RNF43 indicated a higher TNM stage, SSIGN score, and WHO/ISUP grade and short survival in patients with ccRCC. Additionally, RNF43 overexpression suppressed the proliferation, migration, and targeted drug resistance of ccRCC cells, while the knockdown of RNF43 enhanced these characteristics of ccRCC. RNF43 knockdown activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear distribution of YAP. By contrast, RNF43 overexpression showed the opposite effects. Decreasing YAP abolished the effect of RNF43 knockdown in promoting the malignant features of ccRCC. Additionally, restoring RNF43 expression suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC. Furthermore, combining the expression of RNF43 andYAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these indicators alone in assessing the postoperative prognosis of ccRCC patients. In summary, our study identified a novel tumor suppressor, RNF43, which is also a prognostic indicator and potential target for ccRCC potential target for ccRCC.

Sign in / Sign up

Export Citation Format

Share Document