scholarly journals High Expression of JMJD4 Is a Potential Diagnostic and Prognostic Marker of Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Hao Yan ◽  
Yewei Bao ◽  
Zongming Lin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Kidney Cancer ◽  
Renal Cell ◽  
High Expression ◽  
In Vitro Experiments ◽  
Poor Overall Survival ◽  
Cell Renal Cell Carcinoma

Histone demethylase JMJD4 is a burgeoning tumor marker, which has been proven to be associated with colon cancer, but the role it plays in kidney cancer has not yet been investigated. In the present study, we evaluated whether JMJD4 can be a prognostic marker of patients with clear cell renal cell carcinoma (ccRCC) using data from public platform and in vitro experiments. Our results revealed that the expression of JMJD4 is higher in cancerous tissue than in normal tissues ( p < 0.001 ). High expression of JMJD4 is associated with a poor overall survival (OS) of ccRCC as compared with low expression of JMJD4 ( p = 0.015 ). JMJD4 showed significant relevance with M stage ( p = 0.016 ), gender ( p = 0.003 ), OS (0.018), disease-specific survival (DSS) (0.007), and percussion free interval (PFI) (0.041). Univariate and multivariate Cox analyses demonstrated that high JMJD4 expression had independent predictive value for OS in ccRCC patients ( hazard   ratio   HR = 1.563 , 95 % confidence   interval   CI = 1.055 ‐ 2.316 , and p = 0.026 ). Besides, in vitro experiments confirmed that high expression of JMJD4 can significantly promote the invasion ability ( p < 0.001 ), cloning ability ( p < 0.001 ), and proliferation ( p < 0.001 ) of renal cell carcinoma. In summary, high JMJD4 expression may be a prognostic marker in patients with kidney cancer.

scholarly journals High expression of galectin-7 associates with poor overall survival in patients with non-metastatic clear-cell renal cell carcinoma

Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 41986-41995 ◽  
Author(s):  
Jieti Wang ◽  
Yidong Liu ◽  
Yuanfeng Yang ◽  
Zhiying Xu ◽  
Guodong Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
High Expression ◽  
Poor Overall Survival ◽  
Cell Renal Cell Carcinoma

scholarly journals Neuropilin 1 and Neuropilin 2 gene invalidation or pharmacological inhibition reveals their relevance for the treatment of metastatic renal cell carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Aurore Dumond ◽  
Etienne Brachet ◽  
Jérôme Durivault ◽  
Valérie Vial ◽  
Anna K. Puszko ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Metabolism ◽  
Boyden Chamber ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma ◽  
Immunodeficient Mice ◽  
And Migration

Abstract Background Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway. Methods We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs. Results Knock-out of the NRP1 and NRP2 genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients. Conclusions Our study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.

In vitro volatile exometabolome signature of clear cell renal cell carcinoma

2021 ◽  
Vol 350 ◽  
pp. S107
Author(s):  
F.S. Amaro ◽  
J. Pinto ◽  
S. Rocha ◽  
A.M. Araújo ◽  
V.M. Gonçalves ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
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 Construction of a Novel Multigene Panel Potently Predicting Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3471
Author(s):  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Yan Gu ◽  
Mathilda Jing Chow ◽  
Jingyi Peng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Dna Helicase ◽  
Poor Overall Survival ◽  
Cell Renal Cell Carcinoma ◽  
Damage Repair ◽  
Tcga Dataset ◽  
Multigene Panel

We observed associations of IQGAP1 downregulation with poor overall survival (OS) in clear cell renal cell carcinoma (ccRCC). Differentially expressed genes (DEGs, n = 611) were derived from ccRCCs with (n = 111) and without IQGAP1 (n = 397) reduction using the TCGA PanCancer Atlas ccRCC dataset. These DEGs exhibit downregulations of immune response and upregulations of DNA damage repair pathways. Through randomization of the TCGA dataset into a training and testing subpopulation, a 9-gene panel (SigIQGAP1NW) was derived; it predicts poor OS in training, testing, and the full population at a hazard ratio (HR) 2.718, p < 2 × 10−16, p = 1.08 × 10−5, and p < 2 × 10−16, respectively. SigIQGAP1NW independently associates with poor OS (HR 1.80, p = 2.85 × 10−6) after adjusting for a set of clinical features, and it discriminates ccRCC mortality at time-dependent AUC values of 70% at 13.8 months, 69%/31M, 69%/49M, and 75.3%/71M. All nine component genes of SigIQGAP1NW are novel to ccRCC. The inclusion of RECQL4 (a DNA helicase) in SigIQGAP1NW agrees with IQGAP1 DEGs enhancing DNA repair. THSD7A affects kidney function; its presence in SigIQGAP1NW is consistent with our observed THSD7A downregulation in ccRCC (n = 523) compared to non-tumor kidney tissues (n = 100). Collectively, we report a novel multigene panel that robustly predicts poor OS in ccRCC.

scholarly journals High expression of F2RL3 correlates with aggressive features and poor survival in clear cell renal cell carcinoma

2018 ◽  
Vol 9 (18) ◽  
pp. 3400-3406
Author(s):  
Dalong Cao ◽  
Yuanyuan Qu ◽  
Xuan Zhang ◽  
Fujiang Xu ◽  
Shuxian Zhou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
High Expression ◽  
Poor Survival ◽  
Cell Renal Cell Carcinoma
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