scholarly journals AURKB: a promising biomarker in clear cell renal cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7718 ◽  
Author(s):  
Bangbei Wan ◽  
Yuan Huang ◽  
Bo Liu ◽  
Likui Lu ◽  
Cai Lv

BackgroundAurora kinase B (AURKB) is an important carcinogenic factor in various tumors, while its role in clear cell renal cell carcinoma (ccRCC) still remains unclear. This study aimed to investigate its prognostic value and mechanism of action in ccRCC.MethodsGene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database. R software was utilized to analyze the expression and prognostic role ofAURKBin ccRCC. Gene set enrichment analysis (GSEA) was used to analyzeAURKBrelated signaling pathways in ccRCC.ResultsAURKBwas expressed at higher levels in ccRCC tissues than normal kidney tissues. IncreasedAURKBexpression in ccRCC correlated with high histological grade, pathological stage, T stage, N stage and distant metastasis (M stage). Kaplan-Meier survival analysis suggested that highAURKBexpression patients had a worse prognosis than patients with lowAURKBexpression levels. Multivariate Cox analysis showed thatAURKBexpression is a prognostic factor of ccRCC. GSEA indicated that genes involved in autoimmune thyroid disease, intestinal immune network for IgA production, antigen processing and presentation, cytokine-cytokine receptor interaction, asthma, etc., were differentially enriched in theAURKBhigh expression phenotype.ConclusionsAURKBis a promising biomarker for predicting prognosis of ccRCC patients and a potential therapeutic target. In addition,AURKBmight regulate progression of ccRCC through modulating intestinal immune network for IgA production and cytokine-cytokine receptor interaction, etc. signaling pathways. However, more research is necessary to validate the findings.

2020 ◽  
pp. 1-7
Author(s):  
Raviprakash T. Sitaram ◽  
Börje Ljungberg ◽  
Göran Roos ◽  
Marene Landström ◽  
Raviprakash T. Sitaram

Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the signaling components and signaling networks, causing the modification of tumor pathogenesis and prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages, refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxiainducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC. The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its crosstalk with VHL/HIF.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 434-434
Author(s):  
Italia Bongarzone ◽  
Mattia Cremona ◽  
Virginia A. Espina ◽  
Francesca Miccichè ◽  
Silvia Veneroni ◽  
...  

434 Background: There are marked differences in responses to therapy among patients with clear cell renal cell carcinoma (ccRCC), which makes the outcome difficult to predict. This study is aimed to define a new classification system that would elucidate distinctions between carcinomas in order to facilitate selection of the appropriate treatment. We mapped cell signaling pathways in individual renal cell carcinomas and identified different classes based on commonly shared phosphorylation-driven signaling networks. Methods: Laser capture microdissection and reverse-phase protein arrays were used to profile 75 key nodes in 16 primary clear cell renal cancers. These nodes represent many signaling pathways known to be important in tumorigenesis and progression. Results: Statistical analysis revealed significant differences (p <0.05) in signaling levels between two groups of samples, group A (4 samples) and group B (12 samples), for 27 of the 75 endpoints tested. In group A, high activation levels of EGFR, RET, and RASGFR1 converged to activate AKT/mTOR. Group B, showed high phosphorylation levels of ERK1/2 and STAT transcription factors and samples significantly partitioned in two clusters of 7 and 5 cases designated C and D. Group C showed elevated expression of a regulator of autophagy, LC3B; group D showed activation of Src and STAT transcription factors, suggesting the presence of cytokine-mediated cell survival pathways. A DNA copy number analysis was performed on the same samples and the results showed that group B represents some paradigmatic cases of ccRCC, with VHL loss-of-function mutations. Conclusions: The proteins identified appeared to be linked to pathways that are targeted by drugs typically used to treat clear cell renal cell carcinoma. Thus, this type of analysis could be useful for stratifying patients and selecting the best therapeutic approaches.


PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23057 ◽  
Author(s):  
Jonas Sjölund ◽  
Anna-Karin Boström ◽  
David Lindgren ◽  
Sugata Manna ◽  
Aristidis Moustakas ◽  
...  

2021 ◽  
Vol 22 (20) ◽  
pp. 11193
Author(s):  
Eleonora A. Braga ◽  
Marina V. Fridman ◽  
Elena A. Filippova ◽  
Vitaly I. Loginov ◽  
Irina V. Pronina ◽  
...  

The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer—clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis. For the most studied oncogenic lncRNAs, such as HOTAIR, MALAT1, and TUG1, several regulatory axes were identified in ccRCC, demonstrating a number of sites for various miRNAs. Interestingly, the LINC00973/miR-7109/Siglec-15 axis represents a novel agent that can suppress the immune response in patients with ccRCC, serving as a valuable target in addition to the PD1/PD-L1 pathway. Other mechanisms of action of lncRNAs in ccRCC, involving direct binding with proteins, mRNAs, and genes/DNA, are also considered. Our review briefly highlights methods by which various mechanisms of action of lncRNAs were verified. We pay special attention to protein targets and signaling pathways with which lncRNAs are associated in ccRCC. Thus, these new data on the different mechanisms of lncRNA functioning provide a novel basis for understanding the pathogenesis of ccRCC and the identification of new prognostic markers and targets for therapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kaili Chang ◽  
Chong Yuan ◽  
Xueguang Liu

As a type of regulated cell death induced by Ras selective lethal (RSL) compounds such as erasti, ferroptosis is characterized by iron-dependent lipid peroxide accumulation to lethal levels. At present, little is known about the role of ferroptosis-related genes in clear-cell renal cell carcinoma (ccRCC). In the present study, the expression data of ferroptosis-related genes in ccRCC were obtained from the Cancer Genome Atlas (TCGA), and COX regression analysis was performed to construct a risk model of ferroptosis prognostic signature. The GEO database was used to verify the accuracy of the model. The following findings were made: the results reveal that the prognostic signature constructed by 11 ferroptosis genes (CARS, CD44, DPP4, GCLC, HMGCR, HSPB1, NCOA4, SAT1, PHKG2, GOT1, HMOX1) was significantly related to the overall survival (OS) of ccRCC patients based on the lowest Akaike information criterion (AIC); multivariate analysis indicates that ferroptosis-related gene prognostic signature was an independent prognostic factor in ccRCC patients; the calibration curve and c-index value (0.77) demonstrate that the nomogram with the signature could predict the survival of ccRCC patients; and enrichment analysis shows that the high-risk group were enriched in humoral immunity and receptor interaction pathways. The aforementioned findings indicate that the ferroptosis-related gene signature can accurately predict the prognosis of ccRCC patients and provide valuable insights for individualized treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Suhua Gao ◽  
Lei Yan ◽  
Hongtao Zhang ◽  
Xiaoguang Fan ◽  
Xiaojing Jiao ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is one of the most frequent pathological subtypes of kidney cancer, accounting for ~70–75%, and the major cause of mortality is metastatic disease. The difference in gene expression profiles between primary ccRCC tumors and metastatic tumors has not been determined. Thus, we report integrated genomic and transcriptomic analysis for identifying differentially expressed genes (DEGs) between primary and metastatic ccRCC tumors to understand the molecular mechanisms underlying the development of metastases. The microarray datasets GSE105261 and GSE85258 were obtained from the Gene Expression Omnibus (GEO) database, and the R package limma was used for DEG analyses. In summary, the results described herein provide important molecular evidence that metastatic ccRCC tumors are different from primary tumors. Enrichment analysis indicated that the DEGs were mainly enriched in ECM–receptor interaction, platelet activation, protein digestion, absorption, focal adhesion, and the PI3K–Akt signaling pathway. Moreover, we found that DEGs associated with a higher level of tumor immune infiltrates and tumor mutation burden were more susceptible to poor prognosis of ccRCC. Specifically, our study indicates that seven core genes, namely the collagen family (COL1A2, COL1A1, COL6A3, and COL5A1), DCN, FBLN1, and POSTN, were significantly upregulated in metastatic tumors compared with those in primary tumors and, thus, potentially offer insight into novel therapeutic and early diagnostic biomarkers of ccRCC.


2007 ◽  
Vol 177 (4S) ◽  
pp. 214-214
Author(s):  
Sung Kyu Hong ◽  
Byung Kyu Han ◽  
In Ho Chang ◽  
June Hyun Han ◽  
Ji Hyung Yu ◽  
...  

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