Monzó M, Rosell R, Felip E, Astudillo J, Sánchez J J, Maestre J, Martín C, Font A, Barnadas A, Abad A
Laboratory of Molecular Biology of Cancer, Medical Oncology Service, University Hospital Germans Trias i Pujol, Badalona.
J Clin Oncol. 1999 Jul;17(7):2100-4. doi: 10.1200/JCO.1999.17.7.2100.
The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non-small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery.
We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data.
The RT-PCR identified survivin gene transcript in 71 (85. 5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P =.01 by univariate analysis; relative risk, 2. 1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens.
The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.
生存素基因是一种新型凋亡抑制因子,与杆状病毒基因相关,被认为在胎儿发育和癌症中起关键作用。我们推测生存素会在非小细胞肺癌(NSCLC)患者的肿瘤中表达,并试图确定生存素重新表达对接受根治性手术的ⅢA期及以下NSCLC患者临床结局的影响。
我们设计了一种逆转录聚合酶链反应(RT-PCR)检测方法,以研究83例NSCLC肿瘤样本中生存素基因的表达情况,并将结果与相关临床和病理数据进行比较。
RT-PCR在71例(85.5%)肿瘤样本中检测到生存素基因转录本,而在配对的组织病理学正常的肺样本中仅在10例(12%)中检测到。组织学亚型(鳞状细胞癌与非鳞状细胞癌)与生存素基因表达之间无相关性。12例无生存素表达的患者总体生存率明显高于71例有生存素表达的患者(单因素分析P = 0.01;相对风险为2.1)。生存素表达与年龄、性别、吸烟、组织学亚型、肿瘤分化、肿瘤大小或手术标本中纵隔淋巴结转移的存在均无显著相关性。
生存素基因在绝大多数NSCLC肿瘤中表达。我们得出结论,生存素转录本是NSCLC的一个决定性诊断标志物,可能还能提供预后信息,并且作为一种凋亡抑制因子,是癌症治疗的一个重要靶点。