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目的:探讨非小细胞肺癌(NSCLC)EGFR、KRAS基因突变与核苷酸还原酶亚基M1(RRM1)、Ⅲ型β微管蛋白(TUBB3)mRNA表达水平的相关性及其临床意义。方法:69例NSCLC组织标本来自解放军空军总医院胸外科2010年6月至2014年10月手术中从肿瘤中心切取。使用x TAG-液相芯片法检测EGFR、KRAS基因突变,分支DNA-液相芯片法检测RRM1、TUBB3 mRNA表达水平。结果:在69例NSCLC组织样本中,28例为EGFR基因突变(40.6%,28/69),13例为KRAS基因突变(18.8%,13/69),EGFR基因突变与性别(P=0.005)、病理类型(P=0.036)、吸烟史(P=0.029)相关。KRAS基因突变与性别相关(P=0.007)。TUBB3mRNA的表达水平与病理类型相关(P=0.008),RRM1 mRNA的表达水平与患者各临床病理特征无关(P>0.05)。EGFR基因突变与RRM1、TUBB3 mRNA表达水平无关(P>0.05),KRAS基因突变与RRM1 mRNA表达水平无关(P>0.05),KRAS突变型患者TUBB3 mRNA表达水平比KRAS野生型患者高(P<0.05)。结论:在NSCLC患者中,EGFR及KRAS基因的突变状态对评估患者使用吉西他滨及抗微管类药物的疗效有重要意义,尤其在KRAS突变型NSCLC患者中,抗微管类化疗药物的疗效可能不佳,这有利于指导化疗药物方案的制定,促进NSCLC的个体化治疗。
Objective: To investigate the correlation between the expression of EGFR and KRAS gene and the expression of RRM1 and TUBB3 in non-small cell lung cancer (NSCLC) and its clinical significance. Methods: Totally 69 NSCLC specimens were obtained from the Center of Thoracic Surgery from June 2010 to October 2014 in the Department of Thoracic Surgery, People’s Liberation Army Air Force General Hospital. The EGFR and KRAS gene mutations were detected by x TAG-liquid phase microarray and the expression of RRM1 and TUBB3 mRNA was detected by branched DNA-liquid phase microarray. RESULTS: Of 69 NSCLC samples, 28 were EGFR gene mutation (40.6%, 28/69), 13 were KRAS gene mutation (18.8%, 13/69), EGFR gene mutation and sex (P = 0.005) , Pathological type (P = 0.036) and smoking history (P = 0.029). KRAS mutations were associated with gender (P = 0.007). The expression level of TUBB3 mRNA was correlated with the pathological type (P = 0.008). The expression level of RRM1 mRNA was not related to the clinicopathological features (P> 0.05). The mutation of EGFR gene was not related to the expression of RRM1 and TUBB3 mRNA (P> 0.05). The mutation of KRAS gene was not related to the expression of RRM1 mRNA (P> 0.05). The expression of TUBB3 mRNA in KRAS mutant group was higher than that of KRAS wild type ). CONCLUSION: In patients with NSCLC, the mutation status of EGFR and KRAS genes is of great importance in assessing the efficacy of gemcitabine and anti-microtubules in patients. In particular, the efficacy of anti-microtubule chemotherapeutic agents in patients with KRAS mutant NSCLC may not be significant Good, which is conducive to guide the development of chemotherapy drug programs to promote individualized treatment of NSCLC.