Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
Med Oncol. 2012 Sep;29(3):1663-72. doi: 10.1007/s12032-011-0069-8. Epub 2011 Sep 24.
The aim of this study is to elucidate the prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) in completely resected non-small cell lung cancer (NSCLC). One hundred and sixty patients with NSCLC were included in this study. Tumor sections were stained by immunohistochemistry for TS, OPRT, DPD, glucose transporter 1 (Glut1), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), microvessel density (MVD) determinated by CD34, epidermal growth factor receptor (EGFR), phosph-Akt, phosph-mammalian target of rapamycin (mTOR) and p53. TS, OPRT and DPD were positively expressed in 46, 71 and 54%, respectively. The expression of TS and OPRT was significantly higher in patients with non-adenocarcinoma (non-AC) (n = 53) than adenocarcinoma (AC) (n = 107), and DPD expression was higher in adenocarcinoma as compared with non-adenocarcinoma. A positive TS expression was an independent prognostic factor for predicting a poor outcome in patients with AC, but not in those with non-AC. In AC patients, TS expression was significantly associated with advanced stage, lymph node metastases, vascular invasion, Glut1, HIF-1α, angiogenesis, EGFR signaling pathway and p53. In patients with non-AC, TS expression was not closely correlated with outcome and these biomarkers. A positive TS expression was a powerful prognostic factor to predict a poor outcome in completely resected AC patients.
本研究旨在阐明胸苷酸合成酶（TS）、乳清酸磷酸核糖转移酶（OPRT）和二氢嘧啶脱氢酶（DPD）在完全切除的非小细胞肺癌（NSCLC）中的预后意义。本研究纳入了 160 例 NSCLC 患者。采用免疫组织化学法检测肿瘤组织中 TS、OPRT、DPD、葡萄糖转运蛋白 1（Glut1）、缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）、CD34 测定的微血管密度（MVD）、表皮生长因子受体（EGFR）、磷酸化-Akt、磷酸化-哺乳动物雷帕霉素靶蛋白（mTOR）和 p53。TS、OPRT 和 DPD 的阳性表达率分别为 46%、71%和 54%。非腺癌（non-AC）（n=53）患者的 TS 和 OPRT 表达明显高于腺癌（AC）（n=107），而 DPD 表达在腺癌中高于非腺癌。TS 阳性表达是预测 AC 患者预后不良的独立预后因素，但对非 AC 患者则不然。在 AC 患者中，TS 表达与晚期、淋巴结转移、血管侵犯、Glut1、HIF-1α、血管生成、EGFR 信号通路和 p53 显著相关。在非 AC 患者中，TS 表达与预后和这些生物标志物无密切相关性。TS 阳性表达是预测完全切除的 AC 患者预后不良的有力预后因素。
