Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma

Wu, Xiaofen; Chen, Ting; Li, Jie; Ma, Daifu; Zhu, Qingfeng; Lian, Xin

doi:10.1515/med-2016-0043

Cited by 15 publications

(10 citation statements)

References 19 publications

(19 reference statements)

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“…Although in the present study, a decreased VHL mRNA level was observed in tumor samples, this was not found to be associated with the clinicopathological data of the patients or with their outcome or sunitinib treatment. Similar to our results, Xiao-Fen et al reported the underexpression of VHL mRNA in tumor samples from 75 RCC patients (the number of ccRCC cases was not specified) in comparison to normal kidney tissues (23). However, in contrast to our findings, Xiao-Fen et al observed that this decreased expression was associated with cancer TNM progression and tumor size, although the lack of data on the histological subtypes of RCC precludes a direct comparison between their results (23) and ours.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment

et al. 2019

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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer, characterized by the highest mortality rate among other RCC subtypes due to the occurrence of metastasis and drug resistance following surgery. The Von Hippel-Lindau tumor suppressor (VHL)-hypoxia-inducible factor 1 subunit α (HIF1A)/hypoxia-inducible factor 2α (HIF2A)-vascular endothelial growth factor A (VEGFA) protein axis is involved in the development and progression of ccRCC, whereas sunitinib, a tyrosine kinase inhibitor, blocks the binding of VEGFA to its receptor. The aim of the present study was to examine the possible association of the gene expression of VHL, HIF1A, HIF2A, VEGFA and tumor protein P53 ( P53 ) in cancer tissue with the outcome of ccRCC patients who were treated with sunitinib as first-line therapy following nephrec-tomy. A total of 36 ccRCC patients were enrolled, 11 of whom were administered sunitinib post-operatively. Tumor and control samples were collected, and mRNA and protein levels were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. High mRNA and protein expression levels of HIF2A and VEGFA were found to be associated with shorter overall survival (OS) and progression-free survival (PFS) rates, as well as with unfavorable risk factors of cancer recurrence and mortality. Resistance to sunitinib was also observed; the OS and PFS rates were shorter (median OS and PFS: 12 and 6 months, respectively, vs. undetermined). Sunitinib resistance was associated with high HIF2A and VEGFA protein levels (b=0.57 and b=0.69 for OS and PFS, respectively; P<0.001). Taken together, the findings of this study suggest that the protein levels of HIF2A and VEGFA in tumor tissue may serve as independent prognostic factors in ccRCC. ccRCC patients with increased intratumoral HIF2A and VEGFA protein levels, and unaltered VHL protein levels, are not likely to benefit from sunitinib treatment following nephrectomy; however, this hypothesis requires verification by large-scale replication studies.

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Section: Discussionsupporting

confidence: 91%

“…The deregulation of the VHL gene in ccRCC has been widely reported (5,22,23). Studies on the expression patterns of HIF1A (24-28), HIF2A (25-28), VEGFA (5,24,27-29) and P53 (30,31) in ccRCC have revealed variations in terms of cancer progression and/or patient outcome.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment

et al. 2019

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“…Currently, several biomarkers for KIRC that have been detected include von Hippel-Lindau (VHL) [ 8 – 11 ], vascular endothelial growth factor (VEGF) [ 12 – 15 ], carbonic anhydrase IX (CAIX) [ 16 – 18 ], and hypoxia-inducible factor 1 alpha/2 alpha (HIF1a/2a) mutations [ 19 – 21 ], some of which were able to forecast the medical effectiveness and outcomes. Despite that, there have been scarce studies into the molecular biomarkers of KIRP for the prediction of therapeutic efficacy and prognostication.…”

Section: Introductionmentioning

confidence: 99%

Survival prediction of kidney renal papillary cell carcinoma by comprehensive LncRNA characterization

et al. 2017

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Kidney renal papillary cell carcinoma (KIRP) accounts for 10%–15% of renal cell carcinoma (RCC), patients with KIRP tend to have a poor prognosis, and there was a lack of effective prognostic indicators for this type of cancer. Currently, owing to the availability of The Cancer Genome Atlas (TCGA), long non-coding RNAs (LncRNAs) have been discovered to indicate a prognostic value in some tumors. In that regard, we analyzed lncRNA-sequencing data of KIRP in TCGA, and among 780 differentially-expressed lncRNAs, we selected 37 lncRNAs which were able to assist the prognosis. In addition, by using the multivariate cox regression analysis, the prognosis index (PI) that consisted of 7 lncRNAs (including AFAP1-AS1, GAS6-AS1, RP11-1C8.7, RP11-21L19.1, RP11-503C24.1, RP11-536I6.2, and RP11-63A11.1) could predict the progression and outcomes of KIRP with accuracy. More importantly, the PI was considered an independent indicator for prognostication of KIRP. Moreover, having categorized patients with KIRP into cohorts of high risk and low risk, according to the PI, we found that the key genes and pathways varied in these two groups. Overall, these LncRNAs, especially the PI, may be conceived as biomarkers and helpful for determining the different pathological stages for KIRP patients. However, their biological functions need to be further confirmed.

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“…In addition, VHL deficient ccRCC cells prompted β-catenin-driven transcription of AURKA, which was associated with the deformation of primary cilia and induced renal oncogenesis [88]. In sporadic ccRCC, the expression of VHL and JADE-1 was lower; however, in normal conditions, pVHL stabilized JADE-1 that negatively regulated Wnt/β-catenin and promoted apoptosis and renal tumor suppression [89,90].…”

Section: Impact Of Vhl and Hypoxia On Wnt/-catenin Pathway In Ccrccmentioning

confidence: 99%

Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status

Ljungberg¹,

Roos²,

Landström³

et al. 2020

COR

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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.

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Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma

Cited by 15 publications

References 19 publications

Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment

Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment

Survival prediction of kidney renal papillary cell carcinoma by comprehensive LncRNA characterization

Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status

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