Abduljabbar Rezvan, Al-Kaabi Methaq Mueen, Negm Ola H, Jerjees Dena, Muftah Abir A, Mukherjee Abhik, Lai Chun F, Buluwela Laki, Ali Simak, Tighe Patrick J, Green Andrew, Ellis Ian, Rakha Emad
Division of Cancer and Stem Cells, School of Medicine, University Of Nottingham, City Hosital Campus, Nottingham, NG5 1PB, UK,
Breast Cancer Res Treat. 2015 Apr;150(3):511-22. doi: 10.1007/s10549-015-3348-9. Epub 2015 Mar 21.
Peroxisome proliferator-activated receptor-gamma (PPARγ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPARγ is regarded as a differentiation factor and it plays an important role in regulating adipogenesis, cell growth, proliferation and tumour progression. In breast cancer (BC), PPARγ agonists were reported to inhibit proliferation and growth invasion and promote phenotypic changes associated with a less malignant and more differentiated status. This study aims to assess the prognostic and biological roles of PPARγ protein expression in a large cohort of BC patients (n = 1100) with emphasis on the luminal oestrogen receptor (ER) positive class. Immunohistochemistry was used to assess the levels of PPARγ expression in BC series prepared as tissue microarrays (TMAs). PPARγ antibody specificity was confirmed using Western blotting. PPARγ nuclear expression was detected in 79 % of the cases and its expression was positively correlated with the hormonal receptors (ER, progesterone receptor and androgen receptor). PPARγ levels were significantly higher in tumours with lobular subtype, smaller size and lower grade, while HER2-positive, ductal or medullary tumours were associated with lower PPARγ levels. Survival analysis showed that PPARγ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPARγ is an independent predictor of outcome. Higher PPARγ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPARγ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPARγ is a marker of better prognosis and is associated with longer survival.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种被采用的孤儿受体，属于转录因子的核受体超家族。PPARγ被视为一种分化因子，在调节脂肪生成、细胞生长、增殖和肿瘤进展中发挥重要作用。在乳腺癌（BC）中，据报道PPARγ激动剂可抑制增殖、生长侵袭，并促进与恶性程度较低和分化程度较高状态相关的表型变化。本研究旨在评估PPARγ蛋白表达在一大群BC患者（n = 1100）中的预后和生物学作用，重点关注管腔型雌激素受体（ER）阳性类别。采用免疫组织化学方法评估作为组织微阵列（TMA）制备的BC系列中PPARγ的表达水平。使用蛋白质印迹法确认PPARγ抗体的特异性。在79%的病例中检测到PPARγ核表达，其表达与激素受体（ER、孕激素受体和雄激素受体）呈正相关。小叶亚型、较小尺寸和较低分级的肿瘤中PPARγ水平显著更高，而HER2阳性、导管或髓样肿瘤与较低的PPARγ水平相关。生存分析表明，PPARγ在整个系列以及管腔型ER阳性类别中与更好的预后相关。Cox回归模型表明，PPARγ是预后的独立预测因子。在未接受激素治疗的ER阳性肿瘤患者中，较高的PPARγ与更长的生存期相关。PPARγ是与激素受体相关的良好预后标志物。在管腔型BC患者中，PPARγ是预后较好的标志物，与更长的生存期相关。
