VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma

Lessi, Francesca; Mazzanti, Chiara Maria; Tomei, Sara; Cristofano, Claudio Di; Minervini, Andrea; Menicagli, Michele; Apollo, Alessandro; Masieri, Lorenzo; Collecchi, Paola; Minervini, R.; Carini, Marco; Bevilacqua, Generoso

doi:10.1007/s12032-014-0840-8

Cited by 21 publications

(21 citation statements)

References 25 publications

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“…These patients were diagnosed as ccRCC histopathologically for the first time, and had not had any type of anticancer therapy performed before their surgery. The ccRCC tumor of each patient was staged according to the Union for International Cancer Control 2002 classification, and the tumor grading was assessed as previously described [19–21]. The main patient characteristics are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

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Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

Lin

Wang

et al. 2017

Med Sci Monit

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BackgroundCurrent studies indicated that PCDH17 functions as a tumor suppressor, which is frequently inactivated by aberrant promoter methylation in urologic tumors. The main purpose of this study was to investigate the methylation status of PCDH17 in serum and its clinical significance in renal cell carcinoma (RCC).Material/MethodsThe methylation status of PCDH17 in serum samples of 142 RCC patients and 34 controls was evaluated by methylation-specific PCR (MSP). Then we correlated PCDH17 methylation status with the clinicopathologic features of RCC patients and patient outcomes.ResultsWe found that PCDH17 was more frequently methylated in RCC patients than in controls. Moreover, PCDH17 methylation in serum was significantly correlated with advanced stage (p=0.044), higher grade (p=0.019), lymph node metastasis (p=0.008) and tumor progression (p<0.001). In addition, patients with methylated PCDH17 had shorter progression-free survival (p<0.001) and overall survival (p=0.017) than patients without, and PCDH17 methylation in serum was an independent prognostic factor for worse progression-free survival (HR: 4.215, 95% CI: 1.376–9.032, p<0.001) and overall survival (HR: 5.092, 95% CI: 1.149–12.357, p=0.046) of patients with RCC.ConclusionsThe present study indicates that PCDH17 methylation in serum is a frequent event in RCC and associated with risk factors of poor outcomes. Moreover, PCDH17 methylation in serum is a potential prognostic biomarker for patients with RCC after surgery.

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Section: Methodsmentioning

confidence: 99%

“…The main patient characteristics are shown in Table 1. The time to disease progression was defined as the point at which patients had either a local recurrence or a synchronous/metachronous metastasis as detected by computerized tomography (CT) scan [19–21]. The 5-year overall survival data was also collected.…”

Section: Methodsmentioning

confidence: 99%

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

Lin

Wang

et al. 2017

Med Sci Monit

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“…The incidence of renal cell carcinoma (RCC) accounted for about 3% of all adult malignancies, and the mortality of RCC stood up to about 78 000 per year globally . Recently, the presence of RCC presented a gradually rising trend with probabilities of relapse and transfer, and clear cell renal cell carcinoma (KIRC) made up 85% of all RCC cases . Since kidney, located deeply inside the body, was protected by surrounding tissues and organs, it was far from easy to identify lesions that appeared on it.…”

Section: Instructionmentioning

confidence: 99%

LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

Zhang

Chen

et al. 2018

Molecular Carcinogenesis

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This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR‐194‐5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si‐MALAT1, pcDNA‐MALAT1, miR‐194‐5p mimic, miR‐194‐5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK‐8 assay, colony formation assay, and flow cytometry. Dual‐luciferase reporter gene assay was implemented to validate the targeted relationships between MALAT1 and miR‐194‐5p, as well as between miR‐194‐5p and ACVR2B. The results showed that highly expressed MALAT1, ACVR2B, and lowly expressed miR‐194‐5p were associated with larger tumor size (≥4 cm), advanced TNM stage and poor prognosis of KIRC patients, when, respectively, compared with lowly expressed MALAT1, ACVR2B, and highly expressed miR‐194‐5p (P < 0.05). Transfection of pcDNA‐MALAT1, miR‐194‐5p inhibitor, and pcDNA‐ACVR2B conferred the KIRC cells with promoted viability and proliferation, as well as reduced apoptosis (P < 0.05). Treatment of rats with pcDNA‐MALAT1, miR‐194‐5p inhibitor, or pcDNA‐ACVR2B also contributed to larger tumor size growing in them (P < 0.05). Moreover, MALAT1 could directly target miR‐194‐5p to suppress its expression, and ACVR2B was the targeted molecule of miR‐194‐5p (P < 0.05). Finally, ACVR2B could reverse the effects exerted by miR‐194‐5p on viability, proliferation, and apoptosis of KIRC cells (P < 0.05). In conclusion, LncRNA MALAT1/miR‐194‐5p/ACVR2B signaling was regarded as a candidate pathway for modulating KIRC progression.

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“…The same SNP, C1772T, was found at a higher frequency in ccRCC patients than in healthy subjects [71]. …”

Section: Reviewmentioning

confidence: 99%

The role of HIF1α in renal cell carcinoma tumorigenesis

Gudas

Minton

et al. 2014

J Mol Med

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The transcription factor HIF1α is implicated in the development of clear cell renal cell carcinoma (ccRCC). Although HIF1α was initially believed to be essential for ccRCC development, recent studies hypothesize an oncogenic role for HIF2α in ccRCC, but a tumor suppressor role for HIF1α [1], leading to uncertainty as to the precise roles of the different HIF transcription factors in this disease. Using evidence available from studies with human ccRCC cell lines, mouse xenografts, murine models of ccRCC, and human ccRCC specimens, we evaluate the roles of HIF1α and HIF2α in the pathogenesis of ccRCC. We present a convergence of clinical and mechanistic data supporting an important role for HIF1α in promoting tumorigenesis in a clinically important and large subset of ccRCC. This indicates that current understanding of the exact roles of HIF1α and HIF2α is incomplete and that further research is required to determine the diverse roles of HIF1α and HIF2α in ccRCC.

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VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma

Cited by 21 publications

References 25 publications

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

The role of HIF1α in renal cell carcinoma tumorigenesis

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