title: 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.
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. sky7486m@gmail.com.|Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 112, Taiwan. sky7486m@gmail.com.
authors.forename: Hui-Tzu
authors.initials: HT
authors.lastname: Hsu
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan. sungmd@gmail.com.
authors.forename: Ming-Ta
authors.initials: MT
authors.lastname: Sung
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. philamo@gmail.com.|Department of Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 112, Taiwan. philamo@gmail.com.
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan. yjkuo2@vghtpe.gov.tw.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. yjkuo2@vghtpe.gov.tw.
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Kuo
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. chinwenchi@gmail.com.|Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan. chinwenchi@gmail.com.
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. hclee2@ym.edu.tw.
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. cyhsia@vghtpe.gov.tw.|Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan. cyhsia@vghtpe.gov.tw.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Hsia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D047495:PPAR gamma; D034741:RNA, Small Interfering
keywords: PPARγ; hepatocellular carcinoma; macroscopic vascular invasion