Department of Biomedicine and Biotechnology, University of Alcalá, Madrid, Spain.
Department of Pathology, Príncipe de Asturias Hospital, Madrid, Spain.
Aging Male. 2020 Dec;23(5):801-811. doi: 10.1080/13685538.2019.1597840. Epub 2019 Apr 11.
Prostate cancer is one of the most common cancers in the male population. The objective of this investigation was to study the relationship of components of transforming growth factor-B (TGF-β)/phosphoinositide-3-kinases (PI3K)/AKT/mammalian target of rapamycin (mTOR)/nuclear factor kappa B (NF-kB) transduction pathway with clinical-pathological markers. By immunohistochemical methods, we determined the expression of several factors [TGF-β, Transforming Growth Factor B Receptor I (TGFBRI), TGFBRII, PI3K, AKT-Ser, AKT-Thr, mTOR, p-mTOR, inhibitor kB kinase (IKK), pIKK, inhibitor kB (IkB), pIkB, NF-kBp50, and NF-kBp65]. To know their relationship with established classical markers (Preoperative serum prostate specific antigen, pathological tumor stage, clinical tumor stage, Gleason score, perineural invasion, node involvement, positive surgical margins, biochemical progression, and survival) and their importance in the prognosis of biochemical progression, Spearman test, survival analysis, Log-rang test, Kaplan-Meier curves, univariate and multivariate Cox proportional Hazard regression analyses were performed. Spearman analysis showed that there was at least one correlation between TGF-β, TGFBRI, PI3K, pAKT-Thr, p-mTOR, NF-kBp50, and classical markers. Cox multivariate analysis between the prognostic variables (pathological tumor stage, Gleason score, and node involvement) and inmunohistochemical parameters confirmed TGFBR1 and PI3K as a prognostic and independent marker of biochemical progression in prostate cancer. Our results suggest that TGFBR1 and PI3K could be used as useful biomarkers for early diagnosis and prognoses for biochemical recurrence in prostate cancer after radical prostatectomy.
前列腺癌是男性人群中最常见的癌症之一。本研究的目的是研究转化生长因子-β（TGF-β）/磷酸肌醇-3-激酶（PI3K）/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）/核因子 kappa B（NF-κB）转导通路的成分与临床病理标志物的关系。我们通过免疫组织化学方法测定了几种因子（TGF-β、转化生长因子β受体 I（TGFBR1）、TGFBRII、PI3K、AKT-Ser、AKT-Thr、mTOR、p-mTOR、抑制剂 kB 激酶（IKK）、pIKK、抑制剂 kB（IkB）、pIkB、NF-κBp50 和 NF-κBp65）的表达。为了了解它们与已建立的经典标志物（术前血清前列腺特异性抗原、病理肿瘤分期、临床肿瘤分期、Gleason 评分、神经周围侵犯、淋巴结受累、阳性手术切缘、生化进展和生存）的关系及其在生化进展预后中的重要性，我们进行了 Spearman 检验、生存分析、Log-rang 检验、Kaplan-Meier 曲线、单变量和多变量 Cox 比例风险回归分析。Spearman 分析显示，TGF-β、TGFBR1、PI3K、pAKT-Thr、p-mTOR、NF-κBp50 与经典标志物之间至少存在一种相关性。预后变量（病理肿瘤分期、Gleason 评分和淋巴结受累）与免疫组化参数之间的 Cox 多变量分析证实，TGFBR1 和 PI3K 是前列腺癌生化进展的预后和独立标志物。我们的结果表明，TGFBR1 和 PI3K 可作为前列腺癌根治性前列腺切除术后生化复发的早期诊断和预后的有用生物标志物。
