title: The expression of C-FABP and PPARγ and their prognostic significance in prostate cancer.
abstract: The purpose of this study was to test the hypothesis that cooperative interaction between cutaneous fatty acid-binding protein (C-FABP) and peroxisome proliferator-activated receptors (PPAR) promotes the malignant progression of human prostate cancer. The expression of C-FABP, PPARβ/δ and PPARγ was measured by western blot analysis in prostate cell lines and by immunohistochemical staining in tissue sections of benign prostatic hyperplasia (BPH) and prostatic carcinomas. The correlation between the expression of PPARs and C-FABP was assessed. The significance of increased expression of these proteins was analysed with respect to prognosis and compared with those of alternative biomarkers. The expression levels of C-FABP and PPARγ in prostate cancer cell lines and the cytoplasm and nuclei of carcinoma tissues were significantly (Student's t-test, p<0.05) higher compared to those in benign cell lines and BPH tissues. The raised expression level of C-FABP and PPARγ was significantly correlated with the increased combined Gleason scores (GS) of the carcinomas. Enhanced expression of cytoplasmic C-FABP significantly correlated with increased nuclear PPARγ (Student's t-test, p<0.005). While expression of PPARβ/δ in carcinomas did not correlate with patient outcome, the increased levels of both C-FABP and PPARγ were associated with shorter patient survival. Multivariate analysis indicated that C-FABP was independently associated with patient survival, whereas PPARγ was confounded by C-FABP in predicting patient survival. Thus, the increased C-FABP may interact with PPARγ in a coordinated mechanism to facilitate malignant progression in prostatic cancer. Both C-FABP and PPARγ are suitable as prognostic factors to predict the clinical outcome of prostatic cancer patients.
authors.affiliation: Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, L69 3GA, UK.
authors.forename: Farzad S
authors.initials: FS
authors.lastname: Forootan
authors.forename: Shiva S
authors.initials: SS
authors.lastname: Forootan
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Malki
authors.forename: Danqing
authors.initials: D
authors.lastname: Chen
authors.forename: Gandi
authors.initials: G
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Lin
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rudland
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000368:Aged; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma