Colorectal Cancer Expression of Peroxisome Proliferator-Activated Receptor γ (PPARG, PPARgamma) Is Associated With Good Prognosis

Ogino, Shuji; Shima, Kaori; Baba, Yoshifumi; Nosho, Katsuhiko; Irahara, Natsumi; Kure, Shoko; Chen, Li; Toyoda, Saori; Kirkner, Gregory J.; Wang, Y. Lynn; Giovannucci, Edward; Fuchs, Charles S.

doi:10.1053/j.gastro.2008.12.048

Cited by 145 publications

(121 citation statements)

References 53 publications

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“…The multivariate analysis revealed that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors, suggesting that the absence of PPARG expression is a poor prognostic factor for CCR patients. Consistent with our results, Ogino et al [19] and Pancione et al [20] also detected a correlation between the lack of PPARG expression and poor prognosis in patients with CRC. Furthermore, a study performed by Pancione et al [21] demonstrated that lower PPARG levels were associated with increased macrophage infiltration and increased expression of cyclooxygenase-2 and NK-κB, reinforcing the role of PPARG in the antitumor immune response.…”

Section: Discussionsupporting

confidence: 82%

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

et al. 2017

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Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08-6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients.

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Section: Discussionsupporting

confidence: 82%

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

et al. 2017

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“…For instance, in a multivariate analysis of colorectal cancer patients, high counts of eosinophils and MCs predicted longer survival (17). MC tryptases activate the nuclear peroxisome proliferator-activated receptor-γ (PPAR-γ); the expression of PPAR-γ is associated with improved clinical outcome in colon cancer (18). Our findings imply a complex correlation between the increased number of infiltrating MCs and advanced stages of GC patients.…”

Section: Discussionmentioning

confidence: 77%

Increased numbers of gastric-infiltrating mast cells and regulatory T cells are associated with tumor stage in gastric adenocarcinoma patients

Zhao

Cai

et al. 2012

Oncology Letters

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Abstract. Mast cells (MCs) and regulatory T cells (Tregs)are the important components of the inflammatory infiltrating leukocytes in most malignant tumors. Our study was designed to investigate the infiltrating correlation between MCs and Tregs and clarify their prognostic significance in gastric cancer (GC). A total of 60 fresh GC tissues were collected and tumor-infiltrating leukocytes were isolated by gradient centrifugation. Tryptase and Foxp3 were used as markers for MCs and Tregs, respectively. The expression of tryptase and Foxp3 was determined in tumor-infiltrating leukocytes using flow cytometry. The expression of tryptase and Foxp3 were positively correlated. The increased infiltration of MCs correlated significantly with advanced stage of GC. The infiltration of MCs into the tumor may increase the number of Tregs. Tryptase is a promising marker to stratify GC patients into different risk groups.

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“…It also might account for the inefficacity of PPARγ-based therapy, such as 5-aminosalicylates, in the colon of CD patients with colonic involvement compared with UC patients. Whether a maintained DEFB1 expression level might be necessary to account for the protective effect of PPARγ on the development of colorectal cancer will require additional investigation (21,22). In summary, we believe that restoring PPARγ-dependent antimicrobial barrier function might prevent and/or cure inflammatory lesions in the colon of patients with CD.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Peyrin–Biroulet

Beisner

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

137

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Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is essential for intestinal homeostasis in response to both dietaryand microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARγ functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of β-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Pparγ mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARγ-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARγ-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD.β-defensin 1 | Crohn's disease | microbiota | nutrition | PPAR-γ

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Colorectal Cancer Expression of Peroxisome Proliferator-Activated Receptor γ (PPARG, PPARgamma) Is Associated With Good Prognosis

Cited by 145 publications

References 53 publications

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Increased numbers of gastric-infiltrating mast cells and regulatory T cells are associated with tumor stage in gastric adenocarcinoma patients

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

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