PPARγ is functionally expressed in clear cell renal cell carcinoma

Collet, Nicolas; Théoleyre, Sandrine; Rageul, Julie; Mottier, Stéphanie; Jouan, Florence; Rioux‐Leclercq, Nathalie; Fergelot, Patricia; Patard, Jean‐Jacques; Masson, Damien; Denis, Marc G.

doi:10.3892/ijo.2010.891

Cited by 5 publications

(2 citation statements)

References 39 publications

(47 reference statements)

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“…Previous reports indicate that PPARγ is functionally expressed [12] in ccRCC and that increased PPARγ abundance correlates with reduced patient survival [13] , suggesting a possible oncogenic function. In vitro studies investigating the role of PPARγ in ccRCC and other cancers have largely employed natural and synthetic activating ligands including the insulin-sensitizing thiazolidinediones, yet many used super-physiologic concentrations, which can cause off-target effects and confound interpretation of results [14] , [15] .…”

Section: Introductionmentioning

confidence: 99%

PPARγ is dispensable for clear cell renal cell carcinoma progression

Sanchez

Steger²,

Skuli

et al. 2018

Molecular Metabolism

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ObjectiveClear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected in both ccRCC tumors and cell lines, promotes lipid storage in ccRCC and contributes to tumorigenesis in this setting. PPARγ transcriptionally regulates a number of genes involved in lipid and glucose metabolism in adipocytes, yet its role in ccRCC has not been described. The objective of this study was to elucidate endogenous PPARγ function in ccRCC cells.Methods and resultsUsing chromatin immunoprecipitation followed by deep sequencing (ChIP-seq), we found that PPARγ and its heterodimer RXR occupy the canonical DR1 PPAR binding motif at approximately 1000 locations throughout the genome that can be subdivided into adipose-shared and ccRCC-specific sites. CRISPR-Cas9 mediated, loss-of-function studies determined that PPARγ is dispensable for viability, proliferation, and migration of ccRCC cells in vitro and in vivo. Also, surprisingly, PPARγ deletion had little effect on the robust lipid accumulation that typifies the “clear cell” phenotype of kidney cancer.ConclusionOur results suggest that PPARγ plays neither a tumor suppressive nor oncogenic role in advanced ccRCC, and thus single-agent therapeutics targeting PPARγ are unlikely to be effective for the treatment of this disease. The unique cistrome of PPARγ in ccRCC cells demonstrates the importance of cell type in determining the functions of PPARγ.

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Section: Introductionmentioning

confidence: 99%

PPARγ is dispensable for clear cell renal cell carcinoma progression

Sanchez

Steger²,

Skuli

et al. 2018

Molecular Metabolism

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“…GESA pathway analysis of TCGA data reveal multiple differentially expressed pathways in PHYH low expression phenotype. Among these altered pathways, the key peroxisome proliferator-activated receptor gamma (PPARγ) pathway has been shown to be functionally expressed [45] in ccRCC and that increased PPARγ abundance correlates with reduced patient survival [46]. Gluconeogenesis associated pathways pyruvate, and butanoate metabolism have also been shown to be downregulated in kidney cancer [47].…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of PHYH for Overall Survival (OS) in clear cell Renal Cell Carcinoma (ccRCC)

Qiu

Zezhi

Jiang

et al. 2020

Preprint

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This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analysed by Univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene-gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e-19). Kaplan-Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e-05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p=0.025), high stage (StageIII & IV, p=5.604e-05), High level of stage_T (T3-4, p=4.373e-05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p<0.05). Nomogram including Clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway and Renin angiotensin system were differentially enriched in PHYH high expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p<0.05). We suspect that Elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism and RAS might be the key pathways regulated by PHYH in CCRC.

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Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC)

et al. 2021

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This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene–gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e−19). Kaplan–Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e−05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e−05), and high level of stage_T (T3-4, p = 4.373e−05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin–angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.

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PPARγ is functionally expressed in clear cell renal cell carcinoma

Cited by 5 publications

References 39 publications

PPARγ is dispensable for clear cell renal cell carcinoma progression

PPARγ is dispensable for clear cell renal cell carcinoma progression

Prognostic role of PHYH for Overall Survival (OS) in clear cell Renal Cell Carcinoma (ccRCC)

Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC)

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