多基因表达预测可手术ⅢA期非小细胞肺癌新辅助化疗疗效的探讨

背景与目的ⅢA期非小细胞肺癌(non-smallcelllungcancer,NSCLC)新辅助化疗作用仍存在争议,多种基因表达虽然存在一定预后意义,但对预测ⅢA期NSCLC新辅助化疗作用仍未明了。本研究拟探讨多种基因表达对可手术ⅢA期NSCLC新辅助化疗疗效的预测作用。方法在对比ⅢA期NSCLC新辅助化疗与单纯手术疗效的前瞻性随机对照研究中,同期采用免疫组化法,检测抑癌基因p53,癌基因K-ras、HER2,血管内皮生长因子(vascularendothelialgrowthfactor,VEGF),表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR),粘连因子CD44,金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)等蛋白表达。结果新辅助化疗组与单纯手术组的高基因表达率为58.3%比40.6%(P=0.145)。在新辅助化疗患者,组织学病理缓解有效与无效组两年无病生存率及生存期均无显著性差异(P=0.903,P=0.238);高基因表达与病理有效率亦无相关性(P=0.862);高基因与低基因表达组患者的平均无疾病生存分别为(14.1±9.8)月和(27.2±13.6)月(P=0.032),两年无疾病生存率分别为38.1%比46.7%(P=0.607),两组生存曲线出现明显分离,(P=0.093)。结论新辅助化疗患者的高基因表达预示术后更易发生远处转移,对这些患者是否术后加用化疗仍需进一步研究。

Predicting efficacy of neoadjuvant cheomotherapy on resectable stage IIIA non-small cell lung cancer by multi-gene expressions

BACKGROUND & OBJECTIVE: Neoadjuvant chemotherapy for stage IIIA non-small cell lung cancer (NSCLC) remains controversial. The role of the expressions of P53, K-ras, HER2, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), CD44, and matrix metalloproteinase-9 (MMP-9) in predicting efficacy of neoadjuvant chemotherapy on stage IIIA NSCLC is still unclear although they have been found to be related to prognosis. This study was to determine the predictive effect of multi-gene expression on treatment outcome of neoadjuvant chemotherapy for resectable stage IIIA NSCLC. METHODS: Expressions of p53, K-ras, HER2, VEGF, EGFR, CD44, MMP-9 in the patients enrolled in the prospective randomized controlled trial were detected by immunohistochemistry. The treatment efficacies of combination (neoadjuvant chemotherapy combined with surgery) group (36 patients) and surgery alone group (32 patients) were compared. RESULTS: The high gene expression rate was 58.3% in combination group, and 40.6% in surgery alone group(P=0.145). In combination group, no significant difference of disease-free survival rate (P=0.903) and survival time (P=0.238) was found between patients with histopathologic regression and patients without histopathologic regression; high gene expression had no correlation with pathologic regression (P= 0.862); the mean disease-free survival time was significantly lower in high gene expression subgroup than in low gene expression subgroup (14.1+/-9.8) months vs. (27.2+/-13.6) months, P=0.032]; the 2-year disease-free survival rate was 38.1% in high gene expression subgroup, and 46.7% in low gene expression subgroup (P=0.607). CONCLUSIONS: Pathologic regression after neoadjuvant chemotherapy has no correlation with disease-free survival rate and survial time. The high gene expression maybe indicate high risk of postoperative metastasis; the necessity of postoperative chemotherapy needs further study.