scholarly journals The Identification of Zinc-Finger Protein 433 as a Possible Prognostic Biomarker for Clear-Cell Renal Cell Carcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1193
Author(s):  
Simone O. Heyliger ◽  
Karam F. A. Soliman ◽  
Marilyn D. Saulsbury ◽  
Romonia Renee Reams
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Clear Cell ◽  
Histological Grade ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of all urological cancers, with poor prognosis and high mortality. At late stages, ccRCC is known to be mainly resistant to chemotherapy and radiotherapy. Therefore, it is urgent and necessary to identify biomarkers that can facilitate the early detection of ccRCC in patients. In this study, the levels of transcripts of ccRCC from The Cancer Genome Atlas (TCGA) dataset were used to identify prognostic biomarkers in this disease. Analyzing the data obtained indicated that the KRAB-ZNF protein is significantly suppressed in clear-cell carcinomas. Furthermore, ZNF433 is differentially expressed in ccRCC in a stage- and histological-grade-specific manner. In addition, ZNF433 expression was correlated with metastasis, with greater node involvement associated with lower ZNF433 expression (p < 0.01) and with a more unsatisfactory overall survival outcome (HR, 0.45; 95% CI, 0.33–0.6; p = 8.5 × 10−8). Since ccRCC is characterized by mutations in proteins that alter epigenetic modifications and /or chromatin remodeling, we examined the expression of ZNF433 transcripts in ccRCC with wildtype and mutated forms of BAP1, KDMC5, MTOR, PBRM1, SETD2, and VHL. Analysis revealed that ZNF433 expression was significantly reduced in ccRCC with mutations in the BAP1, SETD2, and KDM5C genes (p < 0.05). In addition, the ZNF433 promoter region was highly methylated, and hypermethylation was significantly associated with mRNA suppression (p < 2.2 × 10−16). In silico analysis of potential ZNF target genes found that the largest group of target genes are involved in cellular metabolic processes, which incidentally are particularly impaired in ccRCC. It was concluded from this study that gene expression of ZNF433 is associated with cancer progression and poorer prognosis, and that ZNF433 behaves in a manner that suggests that it is a prognostic marker and a possible tumor-suppressor gene in clear-cell renal cell carcinoma.

scholarly journals Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3

2020 ◽  
Vol 10 ◽  
Author(s):  
Xiang Ju ◽  
Yangyang Sun ◽  
Feng Zhang ◽  
Xiaohui Wei ◽  
Zhenguo Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Histological Grade ◽  
Rapid Development ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P &lt; 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P &lt; 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P &lt; 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

scholarly journals 8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeanette E. Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew L. Kosel ◽  
Daniel Serie ◽  
Paul A. Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas. Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR = 1.6, p = 0.0037) and SSIGN score (OR = 1.9, p = 0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

Downregulation of ACE2 is associated with advanced pathological features and poor prognosis in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Tianjiao Wang ◽  
Fang Xie ◽  
Yun-Hui Li ◽  
Bin Liang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Histological Grade ◽  
Clinical Stage ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma

Aims: The aim of this study was to explore the alteration in ACE2 expression and correlation between ACE2 expression and immune infiltration in clear cell renal cell carcinoma (ccRCC). Methods: The authors first analyzed the expression profiles and prognostic value of ACE2 in ccRCC patients using The Cancer Genome Atlas public database. The authors used ESTIMATE and CIBERSORT algorithms to analyze the correlation between ACE2 expression and tumor microenvironment in ccRCC samples. Results: ACE2 was correlated with sex, distant metastasis, clinical stage, tumor T stage and histological grade. Moreover, downregulation of ACE2 was correlated with unfavorable prognosis. In addition, ACE2 expression was associated with different immune cell subtypes. Conclusion: The authors' analyses suggest that ACE2 plays an important role in the development and progression of ccRCC and may serve as a potential prognostic biomarker in ccRCC patients.

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Robert Jenkins ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1 , PBRM1 , SETD2 and VHL . And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1 , PBRM1 , SETD2 and VHL . Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

scholarly journals Long Noncoding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3

2020 ◽  
Author(s):  
Xiang Ju ◽  
Yangyang Sun ◽  
Feng Zhang ◽  
Xiaohui Wei ◽  
Zhenguo Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Clear Cell ◽  
Histological Grade ◽  
Rapid Development ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Proliferation Ability

Abstract Background: With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Methods: Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. Results: It was found that lncRNA LINC02747 was highly expressed in ccRCC, which was closely related to high TNM stage and histological grade and poor prognosis of patients. The in vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC, and overexpression of miR-608 can inhibit the proliferation of RCC cells. Moreover, it was found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation ability of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation ability of ccRCC cells. Conclusions: LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Paul Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Paul A. Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

2011 ◽  
Vol 58 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Seong H Yoo ◽  
Kyoungbun Lee ◽  
Ji Y Chae ◽  
Kyung C Moon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Exploiting Synthetic Lethal Network for Precision Treatment of Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Zhicheng Liu ◽  
Dongxu Lin ◽  
Linmeng Zhang ◽  
Chen Yang ◽  
Bin Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Large Scale ◽  
Target Genes ◽  
Clear Cell ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Treatment Modalities ◽  
Cell Renal Cell Carcinoma

Abstract Background The emerging of targeted therapies has revolutionized the treatment modalities of advanced clear cell renal cell carcinoma (ccRCC) over the past fifteen years. However, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles of ccRCC cohorts were exploited for conducting an integrative analysis. Method Based on synthetic lethality (SL), a concept that simultaneous losses of two genes cause cell death while a single loss does not, we sought to develop a computational pipeline to infer potential SL partners of ccRCC. Drug response prediction were received from three pharmacological databases to select agents which are likely to be effective in precisely treating patients with target gene mutation. Results We developed a credible method to identify SL pairs and determined a list of 72 candidate pairs which might be utilized to selectively eliminate tumors with genetic aberrations through SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medicine targets for patients with BAP1 mutations. After mapping these target genes to comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potential in BAP1 mutant tumors. Conclusion Overall, our findings provide insight into the overview of ccRCC mutation patterns and offer novel opportunities for improving individualized cancer treatment.

scholarly journals Identification of Six Potentially Long Noncoding RNAs as Biomarkers Involved Competitive Endogenous RNA in Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Kang Yang ◽  
Xiao-fan Lu ◽  
Peng-cheng Luo ◽  
Jie Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cerna Network

Background. Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), usually is representative of metastatic heterogeneous neoplasm that links with poor prognosis, but the pathogenesis of ccRCC remains unclear. Currently, numerous evidences prove that long noncoding RNAs (lncRNAs) are considered as competing endogenous RNA (ceRNA) to participate in cellular processes of tumors. Therefore, to investigate the underlying mechanisms of ccRCC, the expression profiles of lncRNAs, miRNAs, and mRNAs were downloaded from the Cancer Genome Atlas (TCGA) database. A total of 1526 differentially expressed lncRNAs (DElncRNAs), 54 DEmiRNAs, and 2352 DEmRNAs were identified. To determine the connection of them, all DElncRNAs were input to the miRcode database. The results indicated that 85 DElncRNAs could connect with 9 DEmiRNAs in relation to our study. Then, databases of TargetScan and miRDB were used to search for targeted genes with reference to DEmiRNAs. The results showed that 203 out of 2352 targeted genes were identified in our TCGA set. Subsequently, ceRNA network was constructed according to Cytoscape and the targeted genes were functionally analyzed to elucidate the mechanisms of DEmRNAs. The results of survival analysis and regression analysis indicated that 6 DElncRNAs named COL18A1-AS1, WT1-AS, LINC00443, TCL6, AL356356.1, and SLC25A5-AS1 were significantly correlative with the clinical traits of ccRCC patients and could be served as predictors for ccRCC. Finally, these findings were validated by quantitative RT-PCR (qRT-PCR). Based on these discoveries, we believe that this identified ceRNA network will provide a novel perspective to elucidate ccRCC pathogenesis.

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