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在前列腺癌中 C-FABP 和 PPARγ 的表达及其预后意义。

The expression of C-FABP and PPARγ and their prognostic significance in prostate cancer.

机构信息

Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, L69 3GA, UK.

出版信息

Int J Oncol. 2014 Jan;44(1):265-75. doi: 10.3892/ijo.2013.2166. Epub 2013 Nov 5.

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.

摘要

本研究旨在验证以下假说,即皮肤脂肪酸结合蛋白(C-FABP)与过氧化物酶体增殖物激活受体(PPAR)的协同相互作用促进人前列腺癌的恶性进展。通过 Western blot 分析检测前列腺细胞系中 C-FABP、PPARβ/δ 和 PPARγ的表达,通过免疫组织化学染色检测良性前列腺增生(BPH)和前列腺癌组织切片中这些蛋白的表达。评估了 PPARs 与 C-FABP 表达之间的相关性。分析了这些蛋白表达增加的意义,探讨了它们与其他替代生物标志物在预后方面的关系。与良性细胞系和 BPH 组织相比,前列腺癌细胞系及其癌组织的细胞质和细胞核中 C-FABP 和 PPARγ 的表达水平明显升高(Student's t-test,p<0.05)。C-FABP 和 PPARγ 的上调表达水平与癌组织的联合 Gleason 评分(GS)的增加显著相关。细胞质中 C-FABP 的表达增强与核内 PPARγ 的增加显著相关(Student's t-test,p<0.005)。虽然癌组织中 PPARβ/δ 的表达与患者预后无关,但 C-FABP 和 PPARγ 的水平升高与患者生存时间缩短相关。多变量分析表明,C-FABP 与患者生存独立相关,而 PPARγ 在预测患者生存方面受到 C-FABP 的影响。因此,增加的 C-FABP 可能与 PPARγ 以协调的机制相互作用,促进前列腺癌的恶性进展。C-FABP 和 PPARγ 均适合作为预测前列腺癌患者临床结局的预后因素。

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