scholarly journals Analysis of expression alterations of RASSF1A, SEMA3B, RHOA, GPX1, RAR-beta, and NKIRAS1 genes in clear cell carcinoma

Author(s):  
Э.А. Брага ◽  
И.В. Пронина ◽  
В.И. Логинов ◽  
Т.П. Казубская

Гены короткого плеча хромосомы 3 человека в эпителиальных опухолях подвержены частым делециям/амплификациям, мутациям и метилированию, что отражается на уровне их экспрессии. Нами получены данные об изменении при светлоклеточном раке почки уровней экспрессии 6 генов из критичных районов 3 хромосомы человека: SEMA3B, RASSF1A, RAR-beta2, GPX1, RHOA, NKIRAS1. Нами впервые изучена зависимость изменения содержания мРНК этих генов от клинической стадии рака. Анализ изменения экспрессии гена NKIRAS1 при светлоклеточном раке почки проведен впервые. Полученные данные могут быть полезны при выборе прогностических маркеров рака почки. The genes of the short arm of human chromosome 3 in epithelial tumors are subject to frequent deletions, amplifications, mutations, and methylation, which affects their expression. We studied the expression of 6 genes from critical regions of the human chromosome 3 in clear cell renal cell carcinoma, SEMA3B, RASSF1A, RAR-beta2, GPX1, RHOA, and NKIRAS1. For the first time, the dependence of changes in the mRNA content of these genes on the clinical stage of cancer was studied. Analysis of changes in the expression of the NKIRAS1 gene in clear cell renal cell carcinoma was performed for the first time. The obtained data may be useful for selection of prognostic markers of kidney cancer.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8096 ◽  
Author(s):  
Haiping Zhang ◽  
Jian Zou ◽  
Ying Yin ◽  
Bo Zhang ◽  
Yaling Hu ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhanxin Liu ◽  
Zichun Wang ◽  
Xiaoxiong Wang ◽  
Meisong Lu ◽  
Guang Chen

Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, p<0.0001). The result also showed that elevated HOTTIP expression was correlated with more LNM (OR=2.61, 95% CI 1.91-3.58, p<0.0001) and advanced clinical stage (OR=3.57, 95% CI 2.58-4.93, p<0.0001). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dengyong Xu ◽  
Yuzi Xu ◽  
Yiming Lv ◽  
Fei Wu ◽  
Yunlong Liu ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information—normal tissue and ccRCC stages I, II, III, and IV—and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.


2020 ◽  
Author(s):  
Hanyu Rao ◽  
Xiaoxue Li ◽  
Min Liu ◽  
Jing Liu ◽  
Wenxin Feng ◽  
...  

AbstractClear cell renal cell carcinoma (ccRCC) is a largely incurable disease that is highly relevant to epigenetic regulation including histone modification and DNA methylation. SET domain–containing 2 (SETD2) is a predominant histone methyltransferase catalyzing the trimethylation of histone H3 Lysine 36 (H3K36me3) and its mutations are highly relevant to clear cell renal cell carcinoma (ccRCC). However, its physiology role in ccRCC remains largely unexplored. Here we report that Setd2 deletion impairs the β-catenin destruction complex to facilitate ccRCC formation in a c-MYC-generated polycystic kidney disease (PKD) model, which can be relieved by an inhibitor of β-catenin-responsive transcription. Clinically, SETD2 loss is widely observed in ccRCC samples, and negatively correlated with expression of some members of β-catenin destruction complex, but positively correlated with the activation of Wnt/β-catenin signaling. Our findings thus highlight a previously unrecognized role of SETD2-mediated H3K36me3 modification in regulation of Wnt/β-catenin pathway in ccRCC.SummaryOur findings for the first time reveal a previously unrecognized role of the SETD2-mediated H3K36me3 modification in regulation of the Wnt/β-catenin pathway in ccRCC and shed light on the molecular mechanisms underlying the formation of renal cell carcinoma with epigenetic disorders.


2021 ◽  
Author(s):  
Tianjiao Wang ◽  
Fang Xie ◽  
Yun-Hui Li ◽  
Bin Liang

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.


2015 ◽  
Vol 39 (1) ◽  
pp. 72-75 ◽  
Author(s):  
Tomonori Nakamura ◽  
Takeshi Yoshizako ◽  
Hisayoshi Araki ◽  
Mitsunari Maruyama ◽  
Koji Uchida ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Akinori Masuda ◽  
Kyoko Arai ◽  
Daisaku Nishihara ◽  
Tomoya Mizuno ◽  
Hideo Yuki ◽  
...  

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P<0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P<0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P<0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P<0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R=0.550,P<0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.


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