The prognostic value and immunological role of the small mother against decapentaplegic proteins in kidney renal clear cell carcinoma

Background: Kidney renal clear cell carcinoma (KIRC) has the highest incidence rate in renal cell carcinoma (RCC). Although bioinformatics is widely used in cancer, few reliable biomarkers of KIRC have been found. Therefore, continued efforts are required to elucidate the potential mechanism of the biogenesis and progression of KIRC.Methods: We evaluated the expression of tumor necrosis factor (TNF) family genes in KIRC, and constructed a prognostic signature. We validated the signature by another database and explored the relationship between the signature and progression of KIRC. We assessed the prognostic value, immune infiltration, and tumor mutation burden (TMB) of the signature in KIRC.Results: We selected four key genes (TNFSF14, TNFRSF19, TNFRSF21, and EDA) to construct the TNF-related signature. We divided the KIRC patients into high- and low-risk groups based on the signature. Patients with higher risk scores had shorter overall survival and worse prognosis. With another database, we validated the value of the signature. The signature was considered as an independent risk factor. A higher level of risk score was relevant to higher level of immune infiltration, especially T regulatory cells, CD8+ T cells, and macrophages. The signature was also associated with TMB scores, and it may have an effect on assessing the efficacy of immunotherapy.Conclusion: This is the first TNF-family-related signature of KIRC and we demonstrated its effectiveness. It played a significant role in predicting the prognosis of patients with KIRC. It also has the potential to become a powerful tool in guiding the immunotherapy of KIRC patients in clinical practice.

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755: Prognostic Value of Carbonic Anhydrase IX and KI67 as Predictors of Survival for Renal Clear Cell Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)38004-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 200-200 ◽

Cited By ~ 1

Author(s):

Matthew H. Bui ◽

David B. Seligson ◽

Hyung L. Kim ◽

Ken Han ◽

Yunda Huang ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Cell Carcinoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Carbonic Anhydrase Ix

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Expression and Prognostic Role of MEKK3 and pERK in Patients with Renal Clear Cell Carcinoma

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2015.16.6.2495 ◽

2015 ◽

Vol 16 (6) ◽

pp. 2495-2499 ◽

Cited By ~ 4

Author(s):

Qi Chen ◽

Hong-sheng Lu ◽

Mei-fu Gan ◽

Lan-xi Chen ◽

Kai He ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Prognostic Role

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Multiomic Analysis of Cereblon Expression and Its Prognostic Value in Kidney Renal Clear Cell Carcinoma, Lung Adenocarcinoma, and Skin Cutaneous Melanoma

Journal of Personalized Medicine ◽

10.3390/jpm11040263 ◽

2021 ◽

Vol 11 (4) ◽

pp. 263

Author(s):

Hyo Jae Shin ◽

Kyung Jin Lee ◽

Minchan Gil

Keyword(s):

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Cancer Progression ◽

Cutaneous Melanoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Clinical Value ◽

Cancer Types

Cereblon (CRBN) is a component of the E3 ubiquitin ligase complex that plays crucial roles in various cellular processes. However, no systematic studies on the expression and functions of CRBN in solid tumors have been conducted to date. Here, we analyzed CRBN expression and its clinical value using several bioinformatic databases. CRBN mRNA expression was downregulated in various cancer types compared to normal cells. Survival analysis demonstrated that overall survival was significantly positively correlated with CRBN expression in some cancer types including lung adenocarcinoma (LUAD), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM). CRBN expression was downregulated regardless of clinicopathological characteristics in LUAD and KIRC. Analysis of genes that are commonly correlated with CRBN expression among KIRC, LUAD, and SKCM samples elucidated the potential CRBN-associated mechanisms of cancer progression. Overall, this study revealed the prognostic value of CRBN and its potential associated mechanisms, which may facilitate the development of anti-cancer therapeutic agents.

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Identification a ceRNA (XIST/miR-10a-5p/SERPINE1) Axis as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma.

10.21203/rs.3.rs-717299/v1 ◽

2021 ◽

Author(s):

Rui-ji Liu ◽

Zhi-Peng Xu ◽

Shuying Li ◽

Jun-Jie Yu ◽

Bin Xu ◽

...

Keyword(s):

T Cell ◽

Cell Carcinoma ◽

Immune Cell ◽

Clear Cell ◽

Prognostic Biomarker ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Immune Cell Infiltration ◽

Cerna Network

Abstract Background: Kidney cancer is one of the most common malignancies, of which the most aggressive subtype was kidney renal clear cell carcinoma (KIRC), accounting for 80% of them. A growing number of studies point to the involvement of competitive endogenous RNAs in tumor development. However, the role of ceRNA network involved in KIRC remains unclear. Thus, the aim of this study was to investigate the BAP1-associated prognostic ceRNA in KIRC. Methods: We downloaded the RNAseq data from TCGA along with the relevant clinical data. We screened the differentially expressed lncRNAs, miRNAs, mRNAs according to the expression of BAP1 and established a ceRNA network. Results: After comprehensive bioinformatics analysis, we identified the XIST-miR-10a-5p-SERPINE1 ceRNA axis. Next, we confirmed the prognostic role of miR-10a-5p/SERPINE1 in KIRC using survival analysis and Cox regression analysis. To investigate the abnormally high expression of SERPINE1, we performed methylation analysis of SERPINE1 and concluded that the methylation level of SERPINE1 in KIRC was significantly lower than that in normal tissues. Furthermore, to study the role of SERPINE1 in the immune microenvironment in KIRC, we performed immune cell infiltration analysis and found that SERPINE1 expression was positively correlated with the level of multiple immune cell infiltration (CD 4+ T cell, CD 8+ T cell, macrophages, dendritic cells, neutrophils). Conclusion: We constructed a ceRNA (XIST/has-miR-10a-5p/SERPINE1) that can be used as prognostic biomarker of KIRC. Furthermore, we found that miR-10a-5p/SERPINE1 were significantly associated with clinical features and were independent prognostic factors of KIRC.

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Prognostic Value of Long Noncoding RNA DLEU2 and Its Relationship with Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma

International Journal of General Medicine ◽

10.2147/ijgm.s336428 ◽

2021 ◽

Vol Volume 14 ◽

pp. 8047-8064

Author(s):

Shengqiang Fu ◽

Binbin Gong ◽

Siyuan Wang ◽

Qiang Chen ◽

Yifu Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Carcinoma ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Immune Infiltration ◽

Liver Hepatocellular Carcinoma

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Expression of BAG1 is associated with prognosis in kidney renal clear cell carcinoma based on bioinformatics

BMC Cancer ◽

10.1186/s12885-021-07874-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hongrong Wu ◽

Minjing Liu ◽

Yuejun He ◽

Guozhao Meng ◽

Wanbei Guo ◽

...

Keyword(s):

Cell Carcinoma ◽

Molecular Mechanisms ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Neoadjuvant Treatment ◽

Renal Clear Cell Carcinoma ◽

Cox Regression Analysis ◽

Low Expression

Abstract Background BCL2 associated Athano-Gene 1 (BAG1) has been described to be involved in the development and progression of cancer. But the role of BAG1 in kidney renal clear cell carcinoma (KIRC) has remained largely unknown. Methods We performed bioinformatic analysis of data from TCGA and GEO dataset. The role of BAG1 in KIRC was explored by Logistic and Cox regression model. The molecular mechanisms of BAG1 was revealed by GSEA. Results The current study found that the KIRC tumor samples have a low level of BAG1 mRNA expression compared to the matched normal tissues based on TCGA data and GEO databases. Low expression of BAG1 in KIRC was significantly associated with Sex, clinical pathological stage, tumor-node-metastasis (TNM) stage, hemoglobin levels, cancer status and history of neoadjuvant treatment. Kaplan-Meier survival analysis indicated that KIRC patients with BAG1 high expression have a longer survival time than those with BAG1 low expression (p < 0.000). Cox regression analysis showed that BAG1 remained independently associated with overall survival, with a hazard ratio (HR) of 1.75(CI:1.05–2.90; p = 0.029). GSEA indicated that the signaling pathways including fatty acid metabolism and oxidative phosphorylation were differentially enriched in high BAG1 expression phenotype. Conclusions These findings suggested that BAG1 expression may act as a potential favorable prognostic marker and challenging therapeutic target.

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Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01870-5 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Balawant Kumar ◽

Rizwan Ahmad ◽

Giovanna A. Giannico ◽

Roy Zent ◽

Geoffrey A. Talmon ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Ex Vivo ◽

Critical Role ◽

Pdz Domain ◽

Renal Clear Cell Carcinoma ◽

Binding Motif ◽

Loss Of Function

Abstract Background Claudin-2 expression is upregulated in multiple cancers and promotes cancer malignancy. Remarkably, the regulation of claudin-2 expression in kidney cell lines contrasts its reported regulation in other organs. However, claudin-2 role in renal clear cell carcinoma (RCC) remains unknown despite its predominant expression in the proximal tubular epithelium (PTE), the site of RCC origin. Methods Publicly available and independent patient databases were examined for claudin-2 association with RCC. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by Mass spectroscopy, immunoprecipitation and mutational studies, and functional evaluations. Results We show that the significant decrease in claudin-2 expression characterized PTE cells and Ex-vivo cultured mouse kidney subjected to dedifferentiation. Inhibition of claudin-2 was enough to induce mesenchymal plasticity and invasive mobility in these models. Further, a progressive loss of claudin-2 expression associated with the RCC progression and poor patient survival. Overexpression of claudin-2 in RCC-derived cancer cells inhibited tumorigenic abilities and xenograft tumor growth. These data supported a novel tumor-suppressive role of claudin-2 in RCC. Mechanistic insights further revealed that claudin-2 associates with YAP-protein and modulates its phosphorylation (S127) and nuclear expression. The tumor suppressive effects of claudin-2 expression were lost upon deletion of its PDZ-binding motif emphasizing the critical role of the PDZ-domain in claudin-2 interaction with YAP in regulating RCC malignancy. Conclusions Our results demonstrate a novel kidney specific tumor suppressive role for claudin-2 protein and further demonstrate that claudin-2 co-operates with the YAP signaling in regulating the RCC malignancy.

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