Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis

Yu, Ganshen; Lai, Caiyong; Xu, Yunjie; Bu, Chenfeng; Su, Zexuan

doi:10.7314/apjcp.2015.16.11.4665

Cited by 9 publications

(8 citation statements)

References 25 publications

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“…The current results compare favorably with the previous meta-analyses by Yu et al48 and Huang et al49 Yu et al only analyzed whether RASSF1A promoter methylation was correlated with RCC in cancer vs nontumor controls,48 and RASSF1A promoter methylation did not correlate with RCC in tissue samples 48. Our result involving a greater number of eligible studies with a larger population (15 studies with 1,296 tissue samples) showed that RASSF1A promoter methylation was significantly associated with RCC in tissue samples.…”

Section: Discussionsupporting

confidence: 91%

“…Our result involving a greater number of eligible studies with a larger population (15 studies with 1,296 tissue samples) showed that RASSF1A promoter methylation was significantly associated with RCC in tissue samples. In addition, Yu et al48 did not report whether RASSF1A promoter methylation was linked to clinical features (eg, gender, tumor grade, clinical stage, T classification, histologic subtypes, lymph node metastasis, and distant metastasis) and did not include an analysis of overall survival. Huang et al only analyzed whethe RASSF1A promoter methylation was linked to tumor stage (five studies with 252 cases) and grade (four studies with 190 cases), showing that RASSF1A promoter methylation had a borderline significant correlation with tumor stage ( P =0.051) and a significant association with tumor grade ( P =0.001) 49.…”

Section: Discussionmentioning

confidence: 99%

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<em>RASSF1A</em> promoter methylation correlates development, progression, and poor cancer-specific survival of renal cell carcinoma: trial sequential analysis

Zhuang

Chen

Shen

et al. 2018

OTT

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BackgroundThis meta-analysis evaluated the clinicopathologic and prognostic significance of RASSF1A promoter methylation in renal cell carcinoma (RCC).Materials and methodsThe ORs or HRs and their 95% CIs were calculated. Trial sequential analysis was conducted.ResultsTwenty-two articles that included 1,421 patients with RCC and 724 controls were identified. RASSF1A promoter methylation correlated with RCC in tissue, blood, and urine samples. On multivariate analysis, RASSF1A promoter methylation was associated with tumor grade (grade 3–4 vs 1–2: OR=3.59), clinical stage (stage 3–4 vs 1–2: OR=2.15), T classification (pT2–4 vs pT1: OR=2.66), histologic subtypes (papillary vs clear cell: OR=2.91), and cancer-specific survival (HR=1.78), but it was not linked to age, gender, lymph node status, distant metastasis, or overall survival. The Cancer Genome Atlas data also showed that RASSF1A methylation was significantly more likely to be seen in papillary vs clear-cell RCC (OR=23.19).ConclusionRASSF1A promoter methylation may be associated with the development and progression of RCC, as well as poor cancer-specific survival. Methylation was more frequent in papillary vs clear-cell RCC. More studies are needed to confirm these findings in blood or urine samples.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

<em>RASSF1A</em> promoter methylation correlates development, progression, and poor cancer-specific survival of renal cell carcinoma: trial sequential analysis

Zhuang

Chen

Shen

et al. 2018

OTT

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“…Unexpectedly, when we assessed hypermethylation of RASSF1A promoter region in ccRCC, we found a relatively low number of hypermethylated tumor samples, probably due to high DNA heterogeneity in ccRCC tissue as observed by other groups ( 19 , 20 ). Although other authors reported high association of RASSF1A methylation with increased risk of RCC, it has to be noted that this was attributed only to serum DNA but not cancer tissue ( 21 ). In the present study probably the more homogeneous histology of twelve ccRCC metastasized samples resulted in the increased OR similarly to data on serum DNA ( 22 – 24 ).…”

Section: Discussionmentioning

confidence: 94%

Decreased expression of RASSF1A tumor suppressor gene is associated with worse prognosis in clear cell renal cell carcinoma

Kłącz

Wierzbicki

Wrońska

et al. 2015

International Journal of Oncology

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Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70–80%) and is associated with poor prognosis in 40% of cases mainly due to metastasis in the course of the disease. RASSF1, with its isoforms RASSF1A and RASSF1C, is a tumor suppressor gene which has not been fully analyzed in ccRCC yet. The epigenetic downregulation of RASSF1A is commonly associated with promoter hyper-methylation. The aim of the present study was to compare the ccRCC outcomes with the expression of RASSF1A and RASSF1C. Tissues were obtained from 86 ccRCC patients. RASSF1A and RASSF1C mRNA levels were assessed in tumor and matched normal kidney tissue, and in 12 samples of local metastases by quantitative PCR (qPCR). RASSF1A and RASSF1C proteins levels were semi-quantified in 58 samples by western blot analysis and their tissue localization was assessed by immunohistochemistry. Hypermethylation of RASSF1A promoter was measured by high-resolution-melting methylation-specific qPCR. RASSF1A mRNA levels were 4 and 5 times lower in 66% of tumor and 75% metastasized samples. RASSF1A hypermethylation was found in 40% of analyzed T cases. RASSF1A protein expression was 5 or 20 times decreased in 70% tumor and 75% metastatic samples, respectively. RASSF1A hypermethylation, mRNA and protein levels were associated with TNM progression and higher Fuhrman's grading. Decreased RASSF1A expression, hyper-methylation, TNM and Fuhrman's grading were associated with poorer overall survival (OS). Cox hazard ratio (HR) analysis revealed predictor role of RASSF1A mRNA levels on OS and progression-free survival (PFS) in relation to Fuhrman's grading (OS HR=2.25, PFS HR=2.93). RASSF1C levels were increased in ccRCC; no correlations with clinicopathological variables were found. We conclude that RASSF1C gene is not involved in ccRCC progression and we propose that the measurements of RASSF1A mRNA levels in paired tumor-normal kidney tissue could serve as a new prognostic factor in ccRCC.

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“…E2, is known to exert a protective effect beyond its classical endocrine role in several malignant diseases including neurodegenerative disorders, esophageal cancers, colorectal cancers, lung injuries, and coronary artery diseases [ 11 , 40 , 42 , 46 ]. Many cellular functions can be improved by treatment with E2 alone or in combination with its receptors [ 3 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells

Huang

et al. 2016

J Biomed Sci

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BackgroundRenal cell carcinoma (RCC) is an adult malignancy with 2:1 men-to-women ratio, which implies the possible role of sex hormones in RCC carcinogenesis. One of the predominant sex hormones in women before menopause, 17-β-estradiol (or E2), may regulate RCC growth by cellular mechanisms that are still not fully understood.MethodsThe expression levels of E2 receptors (ER1 and ER2) were determined in different RCC cell lines. The DNA damage response induced by E2 was determined by a DNA double-strand break marker γH2AX. To study the possible effect of E2 on oxidative stress response, RCC cells were stained with 2,7-dichlorofluorescein diacetate and analyzed by flow cytometry. Upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) ser40 phosphorylation in response to oxidative stress was detected by immunoblotting. Finally, annexin V/propidium iodide (PI) double staining assay was used to determine E2-induced cellular apoptosis.ResultsVariable expression of ER1 and ER2 were found in the RCC cell lines studied (786-O, A498, and ACHN), in which ACHN and A498 showed highest and lowest ER expression, respectively. In A498 cells, E2 induced DNA double-strand breaks with positive staining of γH2AX. On the other hand, the level of reactive oxidative species were elevated in ACHN cells after E2 treatment. The E2-induced oxidative stress also induced the Ser40 phosphorylation and nuclear translocation of Nrf2. Finally, we also demonstrated that E2 induced apoptosis as revealed by annexin V/PI double staining.ConclusionsIn this study, we demonstrated the cellular effects of E2 on DNA repair, ROS production as well as Nrf2 activation, and apoptosis in RCC cell lines. Together these cellular alterations may contribute to the reduced viability of RCC cells following E2 treatment.

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Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis

Cited by 9 publications

References 25 publications

<em>RASSF1A</em> promoter methylation correlates development, progression, and poor cancer-specific survival of renal cell carcinoma: trial sequential analysis

<em>RASSF1A</em> promoter methylation correlates development, progression, and poor cancer-specific survival of renal cell carcinoma: trial sequential analysis

Decreased expression of RASSF1A tumor suppressor gene is associated with worse prognosis in clear cell renal cell carcinoma

Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells

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