Management and prognostic significance hypercalcemia in renal cell carcinoma

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

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Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.8154 ◽

2007 ◽

Vol 25 (7) ◽

pp. 845-851 ◽

Cited By ~ 33

Author(s):

Thomas Kleinrath ◽

Christoph Gassner ◽

Peter Lackner ◽

Martin Thurnher ◽

Reinhold Ramoner

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Clinical Course ◽

Prognostic Significance ◽

Interleukin 4 ◽

Promoter Polymorphisms ◽

Cox Regression Analysis ◽

Metastatic Rcc

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.

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Prognostic value of C-reactive protein/albumin ratio in renal cell carcinoma: a systematic review and meta-analysis

10.21203/rs.2.17584/v1 ◽

2019 ◽

Author(s):

hualin song ◽

Peng xiang ◽

Zhifu liu ◽

shuai hu ◽

Jie Jin

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis ◽

Prognostic Significance ◽

Clinicopathological Features ◽

C Reactive Protein ◽

Poor Overall Survival ◽

Albumin Ratio ◽

Reactive Protein

Abstract Background: There are a mass of studies declared the prognostic significance of C-reactive protein/albumin ratio (CRP/Alb) in renal cell carcinoma (RCC). Nevertheless, these works are controversial. In our study, we investigate the expression of CRP/Alb in RCC and its role in prognosis and clinicopathological features. Methods: The PubMed, Embase and Cochrane databases were searched systematically for correlative articles published before August 1, 2019. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined according to eligible studies. And we use fixed and random effects models to calculate on the basis of heterogeneity. Results: Six relevant studies were identified in this study, 1959 participants included in total. Our results showed that CRP/Alb was related to poor overall survival (HR=1.86, 95% CI: 1.56-2.21). In addition, CRP/Alb was also associated with tumor stage (OR=3.29, 95% CI: 1.66-6.50), lymph node involvement (OR=3.76, 95% CI: 2.57-5.51), metastasis (OR=5.69, 95% CI: 2.40-13.51), Fuhrman nuclear grade (OR=4.21, 95% CI: 3.14-5.64), pTNM (OR=4.34, 95% CI: 1.94-9.70) and tumor size (WMD=2.26, 95% CI: 1.86–2.67). However, CRP/Alb was not associated with necrosis. Conclusion: Our study illustrates that the higher CRP/Alb expression was correlated with poorer prognosis and more advanced clinicopathological features in RCC patients. High CRP/Alb expression may act as a valuable predictive biomarker for poor prognosis in RCC patients.

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