Association of methylation of genes in the taurine/hypotaurine pathway with worse prognosis in renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15562-e15562
Author(s):  
Andrew Gross ◽  
Michel Choueiri ◽  
John P. Shen ◽  
James Michael Randall ◽  
Trey Ideker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Patient Survival ◽  
Methylation Status ◽  
Tumor Stage ◽  
Methylation Profile ◽  
Advanced Tumor Stage ◽  
Worse Prognosis

e15562 Background: Epigenetic silencing of genes associated with the taurine/hypotaurine pathway has been associated with worse outcome in several tumors such as CDO1 in breast cancer, and GAD1 in prostate cancer. Our objective was to assess the prognostic value of methylation status of genes in the taurine/hypotaurine pathway in patients with renal cell carcinoma (RCC). Methods: We performed an analysis of 283 RCC samples using data from The Cancer Genome Atlas (TCGA). Ten genes belonging to the taurine/hypotaurine metabolic were analyzed using principal component analysis to determine a composite methylation profile of the pathway. A Cox proportional-hazards regression model was then used to determine the association of the composite methylation profile with patient survival. Results: CDO1, GAD2, and GAD1 influenced the outcome of the composite gene the most. Increasing degree of methylation correlated with more advanced tumor stage, and was an independent predictor of overall patient survival. Among patients with localized and locally advanced disease (stages 1-3), high levels of methylation correlated with significantly worse OS (Table). No difference in outcome was noted in patients with metastatic disease. Conclusions: Silencing of genes in the taurine/hypotaurine pathway through methylation is predictive of poorer outcomes in patients with localized RCC. Increasing degree of methylation correlates with tumor stage. Among patients with localized disease and belonging to the same stage, higher degree of methylation correlated with with worse prognosis. Interestingly, this effect is not observed in patients with metastatic disease, indicating the possible activation of other pathways that override the role of the taurine/hypotaurine pathway. [Table: see text]

scholarly journals Significance of Immunohistochemical Expression of Survivin in Renal Cell Carcinoma

2021 ◽  
Vol 6 (3) ◽  
pp. 201-205
Author(s):  
Maisa Hashem Mohammed ◽  
Nagwa Abd El-Sadek Ahmed
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survivin Expression ◽  
Tumor Stage ◽  
Genetic Mutation ◽  
Malignant Neoplasms ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Apoptosis Protein

Background: Evasion of apoptosis is an essential alteration for cellular genetic mutation. Survivin is a member of inhibitor of apoptosis protein (IAP) family. Under normal conditions, Survivin is expressed in embryonic and fetal tissues and markedly diminished in mature, differentiated adult tissues. Survivin was found to be re-expressed in multiple solid and hematological human malignant neoplasms. The purpose of this study was to evaluate the expression of Survivin in renal cell carcinoma (RCC), and to find statistically significant associations between Survivin and the tested Clinicopathological parameters.Methods: 39 patients with RCCs who underwent nephrectomy were included in the study. From each RCC specimen, two tissue sections were obtained; one was stained by H&E stain to determine both RCC phenotype and Fuhrman’s nuclear grades. The second tissue section was immunohistochemically stained by anti-human Survivin antibody. Results: The study revealed statistically significant associations between Survivin expression in RCC specimens and RCC histological types (p =0.002), high tumor grade (p< 0.001) and advanced tumor stage (p< 0.001). Conclusion: The study revealed that Survivin is positively correlated to poorly differentiated RCCs with high Fuhrman’s nuclear grade and advanced tumor stage. 

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy

2020 ◽  
Vol 7 (3) ◽  
pp. 20-25
Author(s):  
Lauren Nahouraii ◽  
Jordan Allen ◽  
Suzanne Merrill ◽  
Erik Lehman ◽  
Matthew Kaag ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Mass ◽  
Tumor Stage ◽  
High Grade ◽  
Renal Masses ◽  
Histologic Heterogeneity ◽  
Adequate Sampling ◽  
Renal Mass Biopsy

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7  cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovas-cular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors pT1b (4–7 cm), RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses <4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (10% vs 2%, P = 0.037), high-grade nuclear elements (31% vs 17%, P = 0.05), and sarcomatoid features (3% vs 0%, P = 0.065) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (16% vs 2%, P < 0.001) and LVI (28% vs 6%, P < 0.001) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.

scholarly journals Low level of Cyclin‐D1 correlates with worse prognosis of clear cell renal cell carcinoma patients

2019 ◽  
Vol 8 (9) ◽  
pp. 4100-4109 ◽  
Author(s):  
Qing‐shui Wang ◽  
Feng Li ◽  
Zi‐qiang Liao ◽  
Ke Li ◽  
Xin‐liu Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Low Level ◽  
Worse Prognosis

scholarly journals Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis

2007 ◽  
Author(s):  
Yoichi Mizutani ◽  
Hiroyuki Nakanishi ◽  
Yong Li ◽  
Hiroki Matsubara ◽  
Kosuke Yamamoto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Xiap Expression ◽  
Worse Prognosis

Capturing Renal Cell Carcinoma Recurrences When Asymptomatic Improves Patient Survival

2019 ◽  
Vol 17 (2) ◽  
pp. 132-138 ◽  
Author(s):  
Suzanne B. Merrill ◽  
Brian S. Sohl ◽  
Ashiya Hamirani ◽  
Erik B. Lehman ◽  
Kathleen K. Lehman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Patient Survival

scholarly journals Immunohistochemical analysis of beta-catenin expression: a probable prognostic marker and potential therapeutic target in renal cell carcinoma

2021 ◽  
Author(s):  
Ayan Kundu ◽  
Anway Sen ◽  
Shouvik Choudhury ◽  
Tapan Kumar Mandal ◽  
Debasish Guha ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Stage ◽  
Low Grade ◽  
Beta Catenin ◽  
High Grade ◽  
Positive Correlation ◽  
Score Difference

Background and aims. Renal cell carcinoma (RCC) seems to be the most aggressive type of genitourinary neoplasm. Down regulation of normal beta-catenin expression contributes to development of RCC, reflecting the role of beta-catenin/Wnt signaling pathway in pathogenesis. This study aims to evaluate the significance of beta-catenin expression and its correlation with the prognostic parameters. Methods. A cross-sectional observational study was carried out in a tertiary care center on 58 RCC cases using variables like histological grade and type, tumor stage, necrosis. Formalin fixed, paraffin-embedded blocks were evaluated for beta-catenin expression by immunohistochemistry using scoring system. Data were analyzed by mean ± SD, χ2 test, Pearson’s correlation test. Results. Membranous score (MS) had a strong negative correlation with tumor stage (r = -0.407, p = 0.044) and grade (r = -0.787, p = <0.001). Mean membranous score difference between low (Stage 1 and 2) vs. high stage (Stage 3 and 4) and low (Grade 1 and 2) vs. high grade (Grade 3 and 4) was statistically significant (p < 0.001). Cytoplasmic score (CS) had positive correlation with tumor stage (r = 0.586; p = 0.002). No significant correlation was evident between cytoplasmic scores and tumor grade, however the mean cytoplasmic score difference between low grade vs. high grade was statistically significant (p < 0.001). Conclusion. Beta-catenin may play a crucial role in the pathogenesis of RCC and has a positive correlation with the biological behavior of this tumor. The important role of beta-catenin as a prognostic parameter and probably a critical evaluator of targeted chemotherapy cannot be overemphasized.

scholarly journals circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Ling Gao ◽  
Xian Shao ◽  
Qingqing Yue ◽  
Weifei Wu ◽  
Xuejuan Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Therapeutic Strategy ◽  
Underlying Mechanism ◽  
Tumor Stage ◽  
Circular Rnas ◽  
The Novel ◽  
Regulatory Functions

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.

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