scholarly journals Bioinformatic gene analysis for potential biomarkers and therapeutic targets of kidney calculi-related renal cell carcinoma

2020 ◽  
Author(s):  
Jun Lu ◽  
Qunlong Liu ◽  
Huan Liu ◽  
Yunfei Xu

Abstract Kidney calculi (KC) is considered to be a potential cause of renal cell carcinoma(RCC)due to urinary retention, hydronephrosis, pyelonephritis, and carcinoma of renal pelvis. We searched co-expressed genes in order to explore the relationships between kidney calculi (KC) and renal cell carcinoma(RCC) and reveal potential biomarkers and therapeutic targets of kidney calculi-related renal cell carcinoma.KC-related differentially expressed genes (DEGs) were identified via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE73680 and GSE117518. Simultaneously, RCC-related DEGs were also identified via bioinformatic analysis GEO datasets GSE14994 and GSE40435. Subsequently, co-DEGs of KC-related RCC were found, and extensive target prediction and network analyses methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in KC and RCC were assessed as well.We identified 832 DEGs in KC and RCC samples. The co-DEGs of VIM,DCN,WNK1 and PXDN coupled with corresponding predicted miRNAs, especially miR-181c-5p and miR-181d-5p may be significantly associated with KC-related RCC. The Co-DEGs of VIM,DCN,WNK1 and PXDN link KC and RCC. Finally, the top 5 miRNAs for each Co-DEGs may be potential signaling pathways for KC-relate RCC, especially miR-181c-5p and miR-181d-5p. Therefore, there is an association between KC and RCC and expression of VIM,DCN,WNK1 and PXDN genes may favor KC-related RCC.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Quan ◽  
Yuchen Bai ◽  
Yunbei Yang ◽  
Er Lei Han ◽  
Hong Bai ◽  
...  

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.


Author(s):  
Haitao Song ◽  
Yanwei Rao ◽  
Gang Zhang ◽  
Xiangbo Kong

MicroRNAs (miRNAs) are emerging as pivotal regulators in the development and progression of various cancers, including renal cell carcinoma (RCC). MicroRNA-384 (miR-384) has been found to be an important cancer-related miRNA in several types of cancers. However, the role of miR-384 in RCC remains unclear. In this study, we aimed to investigate the potential function of miR-384 in regulating tumorigenesis in RCC. Here we found that miR-384 was significantly downregulated in RCC tissues and cell lines. Overexpression of miR-384 significantly inhibited the growth and invasion of RCC cells, whereas inhibition of miR-384 had the opposite effects. Bioinformatic analysis and luciferase reporter assay showed that miR-384 directly targeted the 3′-untranslated region of astrocyte elevated gene 1 (AEG-1). Further data showed that miR-384 could negatively regulate the expression of AEG-1 in RCC cells. Importantly, miR-384 expression was inversely correlated with AEG-1 expression in clinical RCC specimens. Moreover, miR-384 regulates the activation of Wnt signaling. Overexpression of AEG-1 significantly reversed the antitumor effects of miR-384. Overall, these findings suggest that miR-384 suppresses the growth and invasion of RCC cells via downregulation of AEG-1, providing a potential therapeutic target for the treatment of RCC.


2020 ◽  
Author(s):  
Wingkeung Yiu ◽  
Can-Xuan Li ◽  
Jie Chen

Abstract Background: Growing evidence has shown that the type VI collagen alpha chain (COL6A) family involved in the tumorigenesis and progression of diverse malignancies; however, its biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) remain unknown. The study was designed to explore the potential mechanisms and functions of COL6As in ccRCC.Methods: ONCOMINE and GEPIA databases were used to compare the transcriptional expression data of COL6As in ccRCC samples and normal renal samples. UALCAN database was utilized to determine the association between clinicopathological features and COL6As expression. Kaplan–Meier method was employed to determine the prognostic value of COL6As mRNA expression in ccRCC. CBioPortal database was used to investigate the genetic alterations of COL6As in ccRCC. Co-expression analyses, functional enrichment analyses, and gene set enrichment analysis (GSEA) were utilized to explore the potential action mechanisms of COL6As in ccRCC. Finally, we estimated the relationship between COL6As expression with immune cell infiltrates.Results: Upregulated transcriptional COL6A2/COL6A3 expression was observed in ccRCC specimens by comparison with noncancerous renal specimens. Patients with increased COL6A2/COL6A3 mRNA expression have a poor clinical outcome and unfavorable prognosis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses showed that COL6A2/COL6A3 might promote the tumorigenesis and progression of ccRCC by involving in several cancer-related pathways, such as axon guidance, focal adhesion, ECM receptor interaction. Besides, we found that COL6A2/COL6A3 expression was significantly associated with immune infiltration levels in ccRCC.Conclusions: COL6A2 and COL6A3 could act as candidate prognostic biomarkers and therapeutic targets in ccRCC. However, further experimental work was required to validate the conclusions.


2013 ◽  
Vol 62 (12) ◽  
pp. 1757-1768 ◽  
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Consuelo Amantini ◽  
Massimo Nabissi ◽  
Francesca Maines ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1450 ◽  
Author(s):  
Francisca Dias ◽  
Ana Luísa Teixeira ◽  
Inês Nogueira ◽  
Mariana Morais ◽  
Joana Maia ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097714
Author(s):  
Haoran Zhang ◽  
Xingming Zhang ◽  
Xudong Zhu ◽  
Yuchao Ni ◽  
Jindong Dai ◽  
...  

Purpose: It remained unclear whether tyrosine kinase inhibitors (TKIs) related renal impairment had impact on the survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinicopathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria and estimated glomerular filtration rate (eGFR) at baseline and during TKIs treatment were recorded. BUN > 7.1mol/L, eGFR <60 ml/min/1.73m2 and/or proteinuria level > 0.3 g/L were defined as renal impairment. eGFR and proteinuria were furtherly classified into different levels. Treatment outcomes were defined as progression-free survival (PFS) and overall survival (OS). Results: At baseline, the presence of abnormal BUN, eGFR and proteinuria level were observed in 25 (22.7%), 27 (25.5%) and 30 (27.3%) patients, which increased to 46 (41.8%), 55 (50.0%) and 64 (58.2%) respectively after TKIs treatment. In the whole cohort (N = 110), survival analysis suggested that only post-treatment renal impairment was related to survival outcomes. Interestingly, sub-analysis showed that post-treatment eGFR level (p = 0.004), proteinuria (p = 0.014) and eGFR decrease >10% (p = 0.012) and elevated proteinuria compared with baseline (p = 0.006) were statistically correlated with OS among patients without RI at baseline (N = 51). On the contrary, deterioration of renal impairment after TKIs treatment in patients with renal impairment at baseline (N = 59) had no relationship with either PFS or OS. Furthermore, eGFR (p = 0.020) and eGFR decrease >10% (p = 0.016) within 1 year after TKIs therapy were potential biomarkers for OS. Conclusion: Dynamic changes of TKI-induced RI during TKIs treatment, especially eGFR and proteinuria level, could be considered as potential biomarkers predicting survival outcomes of mRCC patients.


2010 ◽  
Vol 106 (7) ◽  
pp. 1081-1087 ◽  
Author(s):  
Benjamin Namdarian ◽  
Kevin V.S. Tan ◽  
Matthew J. Fankhauser ◽  
Thanh T. Nguyen ◽  
Niall M. Corcoran ◽  
...  

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