Twist2 是结直肠癌有价值的预后生物标志物。
Twist2 is a valuable prognostic biomarker for colorectal cancer.
机构信息
Department of Laparoscopy, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438, China.
出版信息
World J Gastroenterol. 2013 Apr 21;19(15):2404-11. doi: 10.3748/wjg.v19.i15.2404.
AIM
To investigate the significance of Twist2 for colorectal cancer (CRC).
METHODS
In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients' clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2.
RESULTS
Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026).
CONCLUSION
Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV.
目的
探讨 Twist2 在结直肠癌（CRC）中的意义。
方法
本研究纳入了 93 例 1999 年 1 月至 2010 年 12 月期间在东方肝胆外科医院接受根治性手术的 CRC 患者。回顾了患者的临床病理特征和随访数据记录。使用福尔马林固定、石蜡包埋的组织块通过免疫组织化学观察 Twist2 和 E-cadherin 的蛋白表达。两位对临床信息不知情的独立病理学家对免疫染色进行半定量评分。总分为 3-6（程度+强度总和）被认为是 Twist2 阳性表达。E-cadherin 的表达分为两个水平（保留和减少）。通过 Cox 比例风险模型分析与预后相关的变量。Kaplan-Meier 分析根据 Twist2 不同表达水平绘制生存曲线。
结果
在 66（71.0%）例样本中观察到 Twist2 阳性表达，主要位于细胞质中。43（46.2%）例样本显示 E-cadherin 表达减少。Twist2 表达与任何临床病理参数之间均无显著相关性。然而，Twist2 阳性表达与 E-cadherin 表达减少显著相关（P=0.040）。多变量分析显示不良 M 期[风险比（HR）=7.694，95%CI：2.927-20.224，P<0.001]和 Twist2 阳性（HR=5.744，95%CI：1.347-24.298，P=0.018）是总体生存（OS）不良的独立危险因素，而 Twist2 阳性（HR=3.264，95%CI：1.455-7.375，P=0.004）、不良 N 期（HR=2.149，95%CI：1.226-3.767，P=0.008）和不良 M 期（HR=10.907，95%CI：4.937-24.096，P<0.001）与不良无病生存（DFS）独立相关。生存曲线显示 Twist2 阴性患者的 OS 和 DFS 明显长于 Twist2 阴性患者，不仅总体如此，而且在不同分期的患者中也是如此，尤其是对于 III 期（P=0.033）和 IV 期（P=0.026）患者的 DFS。
结论
我们的数据首次表明，Twist2 是 CRC 的一个有价值的预后生物标志物，特别是对于 III 期和 IV 期患者。
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