非小细胞肺癌EGFR、KRAS基因突变与RRM1、TUBB3 mRNA表达水平的相关性

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xTAG-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）。TUBB3 mRNA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。

Correlation of EGFR or KRAS mutations with the mRNA expression levels of RRM1 and TUBB3 in non - small cell lung cancer

Objective:To investigate whether EGFR or KRAS gene mutations are correlated with the mRNA ex-pression levels of ribonucleotide reductase subunit M1(RRM1)and class III β - tubulin(TUBB3)in non - small cell lung cancer(NSCLC),and their clinical significance. Methods:A total of 69 NSCLC tissues were from Thoracic Surgery of Air Force General Hospital from June 2010 to October 2014,and were obtained by intraoperative cut. EGFR and KRAS mutations were detected with xTAG liquidchip technology(xTAG - LCT),and mRNA expression levels of RRM1 and TUBB3 genes were detected by branched DNA - liquidchip technology(bDNA - LCT). Results:Of 69 cases NSCLC tissue,28 cases were positive for EGFR mutations(40. 6% ,28 / 69),13 cases were positive for KRAS mutations(18. 8% ,13 / 69). EGFR gene mutations were relevant to gender( P = 0 . 005 ),pathological type(P= 0. 036),smoking(P = 0. 029). KRAS gene mutations were related to gender(P = 0. 007). The mRNA expression levels of TUBB3 genes were related to the pathological type(P = 0. 008). The mRNA expression levels of RRM1 gene were not relevant to clinical and phathological characteristics of NSCLC patients(P > 0. 05). EGFR mutations were not relevant to the mRNA expression levels of RRM1 and TUBB3 gene(P > 0. 05). KRAS mutations were not rele-vant to the mRNA expression levels of RRM1 gene(P > 0. 05). The mRNA expression levels of TUBB3 gene in the NSCLC patients with KRAS mutations were higher than those in patients with wild - type KRAS(P < 0. 05). Conclu-sion:In NSCLC patients,EGFR and KRAS mutation status on the assessment of patients with gemcitabine and anti -microtubule drug efficacy is important,especially in the NSCLC patients with KRAS mutations,the efficacy of anti -tubulin class drugs may be poor. This will help guide development of chemotherapy drugs programs and promote indi-vidualized treatment of NSCLC.