肺癌分子分期的循证医学研究

The Evidence-Based Medicine study of molecular staging for non-small cell lung cancer

目的评估常见的非小细胞肺癌(NSCLC)基因标记物与NSCLC预后的关系,在TNM分期的基础上,进行分子分期,提供有预见性、针对性的个性化量体裁衣式的治疗方案。方法计算机检索PubMed、Ovid、Cochrane library online,查找与NSCLC预后有关的基因标记物的临床随机对照试验、系统评价、Meta分析等,循证评价检索得到的相关文献。结果检索到原始文献83篇,相关参考文献266篇。在NSCLC中检测p53突变率为45%～75%。p53基因突变在Ⅰ～Ⅳ期NSCLC中出现提示预后不良,尤其对Ⅰ期腺癌患者预后意义更强;K-ras在NSCLC中突变率为15%～50%。对于各期NSCLC中的腺癌,应用PCR方法检测到K-ras突变,提示预后不良;血管内皮生长因子(VEGF)在NSCLC中表达率为66%～72%。VEGF是NSCLC的不良预后因素;Cyclin E在NSCLC中表达率为41%～53%。Cyclin E高表达与NSCLC预后不良相关,尤其是Ⅰ～Ⅱ期肺腺癌更有意义;Survivin在NSCLC中表达率为40%～85%。Survivin在Ⅰ～ⅢA期NSCLC高表达提示患者预后不良,且对鳞癌的预后意义更大。结论将p53、K-ras、VEGF、Survivin、Cyclin E组成一个分子分期模型系统进行分子分期是切实可行的。

Objective To study the relationship between common genetic markers and the prognosis for non-small cell lung cancer（NSCLC）,carry out molecular staging at the basis of TNM staging and provide predictive individual treatment plan.Methods Retrieved PubMed,Ovid,Cochrane library online to look up clinic randomized controlled trial,systematic review,Meta-analysis on genetic markers related to prognosis of NSCLC.Results 83 primary articles and 266 related articles involving p53,K-ras,VEGF,Cyclin E,Survivin could be searched.The mutation rate of p53 was 45%-75%,the emerging of p53 gene mutation in NSCLC indicated poor prognosis,especially in stage I lung adenocarcinoma.The mutation rate of K-ras was 15%-50%,detecting K-ras gene mutation in all stage lung adenocarcinoma by PCR indicated poor prognosis.The expression rate of VEGF was 66%-72%,VEGF was a poor prognosis factor for NSCLC.The expression rate of Survivin was 40%-85%,Survivin expressed in NSCLC from stage I to stage ⅢA showed poor prognosis,especially in squamous cell lung carcinoma.The expression rate of Cyclin E was 41%-53%,high expression of Cyclin E in NSCLC was related with poor prognosis,especially squamous cell lung carcinoma from stage I to stage Ⅱ.Conclusions p53,K-ras,VEGF,survivin and Cyclin E were composed to a molecular staging model to carry out molecular staging,which was feasible.