Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Jiangsu, China.
Jpn J Clin Oncol. 2010 Apr;40(4):327-35. doi: 10.1093/jjco/hyp165. Epub 2010 Jan 7.
Survivin and livin, which are members of the inhibitor of apoptosis protein family, regulate both programmed cell death and proliferation. Second mitochondria-derived activator of caspase is thought to regulate apoptosis by antagonizing inhibitor of apoptosis protein. These gene expressions are regarded as prognostic markers in some malignancies. However, result in previous studies of the association of these gene expressions with prognosis of patients with non-small cell lung cancer remains contradictory.
Survivin, livin and second mitochondria-derived activator of caspase mRNA was detected by semi-quantitative reverse transcriptase-polymerase chain reaction in surgical resected tumor specimen from 66 non-small cell lung patients who received adjuvant platinum-based chemotherapy.
Results showed that patients with survivin high expression had significantly shorter tumor-free survival (P = 0.012) and overall survival (P = 0.007) than those with survivin low expression. There was a significant association of second mitochondria-derived activator of caspase high expression in non-small cell lung cancer tissue with longer tumor-free survival (P = 0.021) and overall survival (P = 0.0013). However, livin mRNA expression level had no impact on the tumor-free survival and overall survival of the patients. In multivariate analyses, survivin mRNA high expression (P = 0.033 and P = 0.024) and advanced pathologic stage (P = 0.009 and P = 0.008) were the factors which independently predicted a worse tumor-free survival and overall survival.
Our data suggest that assessment of survivin and second mitochondria-derived activator of caspase mRNA expression may be useful for predicting survival in non-small cell lung cancer patients receiving platinum-based chemotherapy after surgical resection and can provide valuable information for deciding better therapy strategy.
凋亡抑制蛋白家族的成员 Survivin 和 Livin 调节细胞程序性死亡和增殖。线粒体衍生的半胱天冬酶激活剂 2 (second mitochondria-derived activator of caspase,Smac)被认为通过拮抗凋亡抑制蛋白来调节细胞凋亡。这些基因的表达被认为是某些恶性肿瘤的预后标志物。然而,以前关于这些基因表达与非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后相关性的研究结果存在矛盾。
采用半定量逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测 66 例接受含铂辅助化疗的 NSCLC 患者手术切除肿瘤标本中 Survivin、Livin 和 Smac mRNA 的表达。
结果显示,Survivin 高表达患者的无瘤生存期(tumor-free survival,TFS)(P = 0.012)和总生存期(overall survival,OS)(P = 0.007)显著短于 Survivin 低表达患者。Smac 在 NSCLC 组织中的高表达与 TFS(P = 0.021)和 OS(P = 0.0013)的延长显著相关。然而,Livin mRNA 表达水平对患者的 TFS 和 OS 没有影响。多因素分析显示,Survivin mRNA 高表达(P = 0.033 和 P = 0.024)和晚期病理分期(P = 0.009 和 P = 0.008)是独立预测 TFS 和 OS 较差的因素。
我们的数据表明,评估 Survivin 和 Smac mRNA 表达可能有助于预测接受含铂化疗的 NSCLC 患者手术后的生存情况,并为制定更好的治疗策略提供有价值的信息。