Bcl-2 mRNA 表达在可切除的非小细胞肺癌（NSCLC）中的预后作用。

The prognostic role of Bcl-2 mRNA expression in curatively resected non-small cell lung cancer (NSCLC).

机构信息

Department of General-, Visceral- and Tumor Surgery, University of Clinic Cologne, Kerpenerstr. 62, D-50937 Köln, Germany.

出版信息

Lung Cancer. 2010 Oct;70(1):82-7. doi: 10.1016/j.lungcan.2009.12.013. Epub 2010 Jan 12.

DOI:10.1016/j.lungcan.2009.12.013

PMID:20064672

Abstract

BACKGROUND

The effect of the apoptosis related gene Bcl-2 in the pathogenesis in NSCLC remains poorly investigated. Hence the aim of this study was to explore the potential role of Bcl-2 mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC.

METHODS

91 tumor and matching normal tissue samples from patients with NSCLC were analyzed using a quantitative real-time RT-PCR method. The relative Bcl-2 mRNA expression was measured using beta-actin as a reference gene. 45 of the 91 patients had stage I tumors (49%), 19 had stage II (21%) and 27 had stage IIIa (30%). Squamous cell carcinoma was found in 43 patients (47%), adenocarcinoma in 33 (36%) and in large cell carcinoma in 15 (17%) of the patients.

RESULTS

Bcl-2 mRNA expression was detected in 83 (91%) of the investigated tumor samples and in 74 (81%) of the normal lung tissue. The median gene expression was 0.147 in tumor tissue and 0.144 in matching normal lung tissue (p=n.s., Wilcoxon Test). No associations were seen between the tumorous Bcl-2 mRNA expression levels and clinical or histopathologic parameters such as gender, tumor size, TNM stadium and grading, but with tumor histology and smoking. With a follow-up of 85.9 months, the median survival time was 59.7 months. Bcl-2 mRNA expression was significantly associated with patients prognosis (p=0.013, log-rank test). Multivariate regression analysis revealed Bcl-2 expression status and tumor stage as independent prognostic factor.

CONCLUSIONS

Bcl-2 expression in NSCLC is not associated with the pathogenesis of this disease. Our data suggests that Bcl-2 mRNA expression plays a crucial role in the biological behavior of NSCLCs. Quantitation of Bcl-2 expression improves estimation of prognosis and appears to identify patients who will benefit from intensive adjuvant therapy.

摘要

背景

凋亡相关基因 Bcl-2 在非小细胞肺癌（NSCLC）发病机制中的作用仍未得到充分研究。因此，本研究旨在探讨 Bcl-2mRNA 表达作为可切除 NSCLC 患者预后生物标志物的潜在作用。

方法

采用实时定量 RT-PCR 方法分析 91 例 NSCLC 患者肿瘤和配对正常组织标本。以β-肌动蛋白（β-actin）为内参基因，检测相对 Bcl-2mRNA 表达。91 例患者中 45 例为 I 期肿瘤（49%），19 例为 II 期（21%），27 例为 IIIa 期（30%）。43 例患者为鳞癌（47%），33 例为腺癌（36%），15 例为大细胞癌（17%）。

结果

在 83 例（91%）研究肿瘤标本和 74 例（81%）正常肺组织中检测到 Bcl-2mRNA 表达。肿瘤组织中基因表达中位数为 0.147，配对正常肺组织为 0.144（p=n.s.，Wilcoxon 检验）。肿瘤 Bcl-2mRNA 表达水平与性别、肿瘤大小、TNM 分期和分级等临床或组织病理学参数之间无相关性，但与肿瘤组织学和吸烟有关。随访 85.9 个月，中位生存期为 59.7 个月。Bcl-2mRNA 表达与患者预后显著相关（p=0.013，log-rank 检验）。多因素回归分析显示，Bcl-2 表达状态和肿瘤分期为独立预后因素。