Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
J Surg Oncol. 2014 Mar;109(3):255-65. doi: 10.1002/jso.23495. Epub 2013 Nov 19.
Deregulation of apoptosis related genes may be associated with poor outcome in cancer. Aim of the present study was to investigate the prognostic role of expression levels of apoptosis related proteins in stage II and III colon cancer.
From tumor samples of 386 stage II and III colon cancer patients, DNA was isolated and tissue microarrays were constructed. Expression of Bcl-2, Bcl-X, BAX, XIAP, Fas, FasL and c-FLIP was evaluated and PCR-based microsatellite instability analysis was performed.
High FasL expressing tumors were associated with high disease recurrence rates in stage II colon cancer patients overall, as was low Bcl-X expression in microsatellite stable stage II patients. In stage II patients, a multivariable model based on FasL and Bcl-XL expression revealed a significant association with disease free survival (DFS). In stage III colon cancer patients, low Bcl-2, low BAX and low Fas expression levels were associated with worse outcome. In these patients a multivariable model based on angioinvasion and Bcl-2, Fas and FasL expression was significantly associated with DFS.
Stage II patients with low Bcl-X and high FasL protein expression levels and stage III patients with low Fas, high FasL and low Bcl-2 expression could be considered as high risk for disease recurrence.
凋亡相关基因的失调可能与癌症患者的不良预后相关。本研究旨在探讨凋亡相关蛋白表达水平在 II 期和 III 期结肠癌中的预后作用。
从 386 例 II 期和 III 期结肠癌患者的肿瘤样本中分离出 DNA，并构建组织微阵列。评估了 Bcl-2、Bcl-X、BAX、XIAP、Fas、FasL 和 c-FLIP 的表达，并进行了基于 PCR 的微卫星不稳定性分析。
高 FasL 表达的肿瘤与 II 期结肠癌患者的高疾病复发率相关，微卫星稳定的 II 期患者的低 Bcl-X 表达也是如此。在 II 期患者中，基于 FasL 和 Bcl-XL 表达的多变量模型与无病生存（DFS）显著相关。在 III 期结肠癌患者中，低 Bcl-2、低 BAX 和低 Fas 表达水平与预后不良相关。在这些患者中，基于血管侵犯以及 Bcl-2、Fas 和 FasL 表达的多变量模型与 DFS 显著相关。
低 Bcl-X 和高 FasL 蛋白表达水平的 II 期患者以及低 Fas、高 FasL 和低 Bcl-2 表达水平的 III 期患者可被视为疾病复发的高风险患者。
