Relationship between visceral adipose tissue and genetic mutations (VHL and KDM5C) in clear cell renal cell carcinoma

Objective: The excessive amount of adipose tissue, mainly visceral, determines adiposopathy. With respect to oncogenesis, visceral adipose tissue (VAT) releases secretes adipokines, proinflammatory citokines and growth factors, considered mediating molecules in the development of obesity-related tumors. In this study, we quantify VAT in male patients with clear cell renal cell carcinoma (ccRCC) subgrouped according to the presence or absence of peritumoral collateral vessels. Methods: in this retrospective study, we enrolled 141 male caucasian patients divided into 2 groups: the ccRCC group (n = 106) composed of patients with ccRCC and control group (n = 35). The ccRCC group was further divided into two subgroups: the ccRCCa subgroup which showed absence of collateral vessels (n = 48) and ccRCCp subgroup with collateral vessels (n = 58). Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in the groups and subgroups. VAT/SAT ratio was calculated for each subject. Results: Statistically significant differences were obtained between ccRCC group and control group for TAT area (p < 0.005), VAT area (p < 0.005) and SAT area (p = 0.01). Between ccRCCa subgroup and control group for TAT area (p < 0.001), VAT area (p = 0.005) and SAT area (p = 0.001). Between ccRCCp subgroup and control group for TAT area (p = 0.01) and VAT area (p = 0.01). Conclusion: This study confirms the increase of abdominal, especially visceral, adipose tissue in ccRCC patients and demonstrates a significant VAT accumulation in both categories of patients with and without peritumoral collateral vessels. Advances in knowledge: Visceral adiposity is present in patients with ccRCC regardless the presence of peritumoral collateral vessels, with surprisingly stronger results in the ccRCCa subgroup.

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Perirenal fat surface area and visceral adipose tissue are associated with different pathological subtypes of renal cell carcinoma or oncocytoma

European Urology Supplements ◽

10.1016/s1569-9056(17)31874-2 ◽

2017 ◽

Vol 16 (10) ◽

pp. e2739

Author(s):

D. Garcia-Rojo ◽

M. Capdevila ◽

A. Prera ◽

C. Abad ◽

A. Malet-Munte ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adipose Tissue ◽

Cell Carcinoma ◽

Surface Area ◽

Visceral Adipose Tissue ◽

Renal Cell ◽

Visceral Adipose ◽

Pathological Subtypes ◽

Perirenal Fat

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Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.571 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 571-571

Author(s):

Wen-Hao Xu ◽

Yuan-Yuan Qu ◽

Jun Wang ◽

Hai-Liang Zhang ◽

Dingwei Ye

Keyword(s):

Renal Cell Carcinoma ◽

Adipose Tissue ◽

Cell Carcinoma ◽

Mrna Expression ◽

Correlation Coefficient ◽

Visceral Adipose Tissue ◽

Renal Cell ◽

Poor Prognosis ◽

Cd36 Expression ◽

Visceral Adipose

571 Background: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by MRI. Pearson’s correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Cox regression analysis were developed to address the influence of independent factors on prognostic value. Gene Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from TCGA database. Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC tissues, and was found significantly increased in patients with advanced TNM stage ( p= 0.003, p< 0.001, p< 0.001), and high VAT% ( p= 0.004). Pearson’s correlation coefficient indicated CD36 amplification positively correlated with BMI ( r= 0.117, p= 0.025), VAT% ( r= 0.465, p< 0.001), while negatively with SAT ( r= -0.296, p= 0.002). Furthermore, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with HR of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases whose MRI scans were available, VAT was significantly correlated with poor PFS and OS. Significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, angiogenesis and TGF-β signaling pathways. Conclusions: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.

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Fatty acid synthase (FASN), a novel signature for visceral adipose tissues, regulates proliferation, migration and predicts prognosis of clear cell renal cell carcinoma

10.21203/rs.2.24247/v1 ◽

2020 ◽

Author(s):

Wen-Hao Xu ◽

Aihetaimujiang Anwaier ◽

Hong-Kai Wang ◽

Jun Wang ◽

Wen-Kai Zhu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adipose Tissue ◽

Mrna Expression ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Normal Tissues ◽

Hazard Ratios ◽

And Migration ◽

Visceral Adipose

Abstract Background: Growing evidence has indicated obesity one of the important etiological indicators of clear cell renal cell carcinoma (ccRCC). This study aims to investigated FASN mRNA expression in anthropometric adipose tissue, and elucidate prognostic value and potential functions in ccRCC patients. Methods: Transcriptional expression profiles was obtained from 380 paired ccRCC and adjacent normal tissues from Fudan University Shanghai Cancer Center (FUSCC) and 533 ccRCC samples from the Cancer Genome Atlas (TCGA) cohort. The visceral adipose tissue (VAT) and the subcutaneous adipose tissue (SAT) at the level of the umbilicus were measured using magnetic resonance imaging. The Kaplan-Meier method and log-rank test, with cooperation from Cox regression analysis, were used in survival analysis. Subsequently, we transiently transfected FASN plasmid into A498 and 786O cells, and investigated the role of FASN in ccRCC cell proliferation, apoptosis and migration in vitro. Related hub gens, functional annotations and significant signal pathways were predicted using integrated bioinformatics. Results: FASN mRNA expression was significantly higher in tumor than normal tissues in 913 ccRCC patients from FUSCC and TCGA cohorts. In addition, increased FASN mRNA expression was significantly relevant to advanced T stage ( p <0.001), N stage ( p =0.019), and AJCC stage ( p =0.002). Pearson’s correlation coefficient indicated that FASN amplification positively correlated with VAT% ( r =0.772, p <0.001). VAT% was significantly correlated with poor PFS and OS, with hazard ratios of 2.066 (1.113-7.261, p =0.028) and 2.773 (1.168-8.974, p =0.023) in FUSCC. Meanwhile, ccRCC patients with elevated FASN expression significantly responded for poor PFS and OS, with hazard ratios of 1.529 (1.135-2.061, p =0.005) and 1.450 (1.030-2.041, p =0.033). Next, after transfection efficiency was verified in A498 and 786O cells, we found transient inhibition and overexpression of FASN significantly regulates cells proliferation and migration abilities, and inhibition of FASN displayed higher apoptotic rate in ccRCC cells. Conclusion: In conclusion, this study demonstrated that FASN mRNA expression is positively related with aggressive proliferation, migration progression and predicts prognosis of ccRCC. In addition, we first reveal that elevated FASN mRNA expression is significantly correlated with abdominal obesity distribution, especially VAT%, which also is a significant predictor of poor prognosis in patients with ccRCC.

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Genetic mutations associated with metastatic clear cell renal cell carcinoma

Oncotarget ◽

10.18632/oncotarget.7473 ◽

2016 ◽

Vol 7 (13) ◽

pp. 16172-16179 ◽

Cited By ~ 3

Author(s):

Zhongjun Li ◽

Ping Hao ◽

Qingjian Wu ◽

Fengjie Li ◽

Jiang Zhao ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Genetic Mutations ◽

Cell Renal Cell Carcinoma

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Influence of Contrast Administration on Computed Tomography-Based Analysis of Visceral Adipose and Skeletal Muscle Tissue in Clear Cell Renal Cell Carcinoma

Journal of Parenteral and Enteral Nutrition ◽

10.1002/jpen.1067 ◽

2018 ◽

Vol 42 (7) ◽

pp. 1148-1155 ◽

Cited By ~ 8

Author(s):

Michael T. Paris ◽

Helena F. Furberg ◽

Stacey Petruzella ◽

Oguz Akin ◽

Andreas M. Hötker ◽

...

Keyword(s):

Computed Tomography ◽

Skeletal Muscle ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Muscle Tissue ◽

Renal Cell ◽

Clear Cell ◽

Contrast Administration ◽

Cell Renal Cell Carcinoma ◽

Visceral Adipose

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Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers12123602 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3602

Author(s):

Jee Soo Park ◽

Kyo Chul Koo ◽

Doo Yong Chung ◽

Sun Il Kim ◽

Jeongho Kim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Body Composition ◽

Adipose Tissue ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Univariate Analysis ◽

Progression Free Survival ◽

Visceral Adiposity ◽

Cell Renal Cell Carcinoma

Sunitinib is a first-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about the predictive factors of sunitinib-induced dose-limiting toxicity (DLT) in Asian populations. We investigated whether body composition predicts sunitinib-induced DLT. We retrospectively reviewed sunitinib-treated Korean patients with clear cell mRCC from eight institutions. Body composition was measured using computed tomography. DLT was defined as any adverse event leading to dose reduction or treatment discontinuation. Univariate analysis was used to compare body composition indices, and logistic regression analyses were performed for factors predicting early DLT. Overall, 111/311 (32.5%) of patients experienced DLT. Significant differences were observed in the subcutaneous adipose tissue index (SATI; p = 0.001) and visceral adipose tissue index (VATI; p < 0.001) between patients with and without DLT. Multivariate analyses revealed that VATI (odds ratio: 1.013; p = 0.029) was significantly associated with early DLT. Additionally, 20% of patients who had a body mass index (BMI) greater than 23 kg/m2 and a low VATI experienced DLT, whereas 34.3% of the remaining groups had DLT (p = 0.034). Significant differences were observed for median progression-free survival (13.0 vs. 26.0 months, respectively; p = 0.006) between patients with low and high VATI. Visceral adiposity was a significant predictor of sunitinib-associated DLT and survival. Patients with a low VATI and a BMI greater than 23 kg/m2 experienced lower DLTs.

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