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Bcl-2 和细胞周期蛋白 A2 对 I 期非小细胞肺癌不良无复发生存的协同作用。

Synergistic effect of Bcl-2 and cyclin A2 on adverse recurrence-free survival in stage I non-small cell lung cancer.

机构信息

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea.

出版信息

Ann Surg Oncol. 2013 Mar;20(3):1005-12. doi: 10.1245/s10434-012-2727-2. Epub 2012 Nov 1.

DOI:10.1245/s10434-012-2727-2

PMID:23115005

Abstract

BACKGROUND

The prognostic significance of cyclin A2 overexpression in non-small cell lung cancer (NSCLC) is controversial.

METHODS

To understand the effect of cyclin A2 on recurrence in NSCLC, we retrospectively analyzed the expression of Bcl-2, cyclin A2, E-cadherin, Ki-67, and p53 using immunohistochemistry in 635 NSCLCs.

RESULTS

Overexpression of cyclin A2 was found in 466 (73%) of 635 NSCLCs, and recurrence occurred in 291 (46%) of 635 NSCLCs with a median follow-up of 5.4 years. The relationship between recurrence and cyclin A2 overexpression was not homogenous by pathologic stage (Breslow-Day test for homogeneity, P = 0.007). Overexpression of cyclin A2 was associated with poor recurrence-free survival (RFS) in 374 stage I NSCLCs (P = 0.02), and RFS was worse in patient with negative expression of Bcl-2 than those with positive expression of Bcl-2. Cox proportional hazard analysis showed that stage I NSCLC patients with overexpression of cyclin A2 and negative expression of Bcl-2 had poorer RFS (hazard ratio = 3.86, 95% confidence interval = 1.07-15.77; P = 0.03) than those with normal expression of cyclin A2 and Bcl-2, after adjusting for age, adjuvant radiotherapy, and histology. Neural network and generalized linear model including cyclin A2 and Bcl-2 showed best performance in the prediction of recurrence; error rates for neural network and generalized linear model were 15% and 12%, respectively.

CONCLUSIONS

Negative effect of cyclin A2 on RFS in stage I NSCLC was aggravated by negative expression of Bcl-2.

摘要

背景

细胞周期蛋白 A2（cyclin A2）在非小细胞肺癌（NSCLC）中的过表达的预后意义存在争议。

方法

为了了解 cyclin A2 对 NSCLC 复发的影响，我们使用免疫组织化学法对 635 例 NSCLC 中 Bcl-2、cyclin A2、E-钙黏蛋白、Ki-67 和 p53 的表达进行了回顾性分析。

结果

在 635 例 NSCLC 中，有 466 例（73%）存在 cyclin A2 过表达，在中位随访 5.4 年时，有 291 例（46%）发生了复发。通过病理分期（Breslow-Day 检验用于检验同质性，P=0.007）发现，复发与 cyclin A2 过表达之间的关系并不均匀。在 374 例 I 期 NSCLC 中，cyclin A2 过表达与无复发生存期（RFS）不良相关（P=0.02），Bcl-2 阴性表达患者的 RFS 比 Bcl-2 阳性表达患者差。Cox 比例风险分析显示，I 期 NSCLC 患者 cyclin A2 过表达且 Bcl-2 阴性表达者的 RFS 较差（危险比=3.86，95%置信区间=1.07-15.77；P=0.03），与 cyclin A2 和 Bcl-2 表达正常的患者相比，在校正年龄、辅助放疗和组织学后。包含 cyclin A2 和 Bcl-2 的神经网络和广义线性模型在预测复发方面表现最佳；神经网络和广义线性模型的错误率分别为 15%和 12%。