Peroxisome Proliferator-Activated Receptor γ Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor that regulates cellular lipid and glucose metabolism and also plays an inhibitory role in various cancers. However, the role of PPARγ in hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the prognostic value of PPARγ in HCC and its role in inhibiting tumor progression, namely, HCC cell growth, migration, and angiogenesis. Immunohistochemical PPARγ staining was examined in 83 HCC specimens to investigate the clinicopathological correlations between PPARγ expression and various parameters. The functional role of PPARγ was determined via PPARγ overexpression and knockdown in HCC cells. Patients with low HCC tissue PPARγ expression were significantly younger (p = 0.006), and exhibited more tumor numbers (p = 0.038), more macroscopic vascular invasion (MVI) (p = 0.008), and more advanced TNM (size of primary tumor, number of regional lymph nodes, and distant metastasis) stages at diagnosis (p = 0.013) than patients with high HCC tissue PPARγ expression. PPARγ knockdown increased HCC cell growth, migration, and angiogenesis, while PPARγ overexpression reduced HCC cell growth, migration, and angiogenesis. These results suggest that low PPARγ expression is an independent predictor of more MVI in HCC patients. PPARγ contributes to the suppression of HCC cell growth, migration, and angiogenesis. Therefore, PPARγ may be a therapeutic target in HCC patients.

Relationship of <em>PPARG</em>, <em>PPARGC1A</em>, and <em>PPARGC1B</em> polymorphisms with susceptibility to hepatocellular carcinoma in an eastern Chinese Han population

“…PPARG has been considered a HCC suppressor that contributes to the suppression of HCC-cell growth, angiogenesis, and migration. 36 – 39 These primary results indicate that PPARG plays an important role in tumor suppression and may be a therapeutic target in HCC. 36 An SNP can lead to abnormal expression or to the generation of a defective form of the protein.…”

“… 36 – 39 These primary results indicate that PPARG plays an important role in tumor suppression and may be a therapeutic target in HCC. 36 An SNP can lead to abnormal expression or to the generation of a defective form of the protein. Therefore, SNPs may be associated with the development of disease.…”

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial

“…PPARγ is heterogeneously expressed in HCC cells [ 29 ]. Corresponding agonists act growth inhibitory, pro-apoptotic via up-regulation of tumor suppressor genes, e.g., PTEN, or a putative tumor suppressor gene, the growth differentiation factor-15 [ 30 ] and promote accumulation of p27(Kip1) [ 31 ].…”

THE MODEL OFPPARγDOWNREGULATED SIGNALING IN PSORIASIS

“…Also, STAT3 is described as an important linkage between keratinocytes and immune cells (Chowdhari and Saini, 2014). Previously the expression of STAT3 was shown to be repressed due to PPARγ activation (Hsu et al, 2016). STAT3 may also act as a regulator of PPARγ expression however it is not clear whether with positive or negative effect (Tuna et al, 2014).…”