EBV相关胃癌ras基因突变及法尼基转移酶β-亚单位基因的表达

Ras mutation and expression of farnesyltransferase β mRNA in Epstein-Barr virusassociated gastric carcinoma

目的:探讨EBV相关胃癌(EBVaGC)、EBV阴性胃癌(EBVnGC)及相应癌旁组织中ras基因突变和法尼基转移酶(FTase)的表达意义.方法:应用PCR-RFLP技术检测EBVaGCs13例、EBVnGCs45例以及相应癌旁组织58例中H-ras12和K-ras12,13密码子点突变情况;RT-PCR技术检测FTaseβ亚单位mRNA的表达水平.结果:共检测到H-ras12位点突变2例,突变率为3.45%(2/58),均发生在EBVnGCs,未发现K-ras12和13密码子点突变.58例癌组织中FTaseβ亚单位mRNA表达水平为0.93±0.39,癌旁组织中FTaseβ亚单位mRNA表达水平为0.78±0.26,两者有显著性差异(t=2.44,P=0.02).EBVaGCs组织中FTaseβ亚单位mRNA表达水平为0.80±0.19,EBVnGCs组织中FTaseβ亚单位mRNA表达水平为0.96±0.43,两者无显著性差异(t=1.93,P=0.06);EBVaGCs和癌旁组织中FTaseβ亚单位mRNA表达水平无显著性差异(t=0.54,P=0.60);EBVnGCs和癌旁组织中FTaseβ亚单位mRNA表达水平有显著性差异(t=2.39,P=0.02);2例BHRF1阳性和11例BHRF1阴性EBVaGCs组织中FTaseβ亚单位mRNA表达水平无显著性差异(t=0.26,P=0.80);6例BARF1阳性和7例BARF1阴性EBVaGCs组织中FTaseβ亚单位mRNA表达水平亦无显著性差异(t=1.59,P=0.14).结论:胃癌组织ras基因突变率较低,胃癌组织中FTaseβ亚单位mRNA明显高于癌旁组织.EBVaGC组织中ras基因突变、FTaseβ亚单位表达与EBV感染无明显相关性.

AIM： To investigate ras gene mutations and farnesyltransferase （FTase） β mRNA expression in Epstein-Barr virus（EBV）-associated gastric carcinoma （EBVaGC）, EBV-negative gastric carcinoma （EBVnGC） with matched clinicopathological parameters and corresponding adjacent tissues of gastric carcinoma. METHODS： The mutations of ras gene were detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and the expression of FTase β mRNA was tested by reverse transcription PCR （RT-PCR） in β EBVaGCs, 45 EBVnGCs with matched clinicopathological parameters and 58 corresponding adjacent tissues of gastric carcinoma.RESULTS： H-ras mutation at codon 12 was detected in 2（3.45%） cases of gastric carcinomas, both of which were EBVnGCs. No K-ras mutations occurred at codon 12 and 13 in all cases. The level of FTase β mRNA expression was 0.93 ± 0.39 in gastric carcinomas and 0.78 ± 0.26 in cor- responding adjacent tissues, respectively. The difference between the two groups was significant （t = 2.44, P = 0.02）. The level of FTase β mRNA expression was 0.80 ± 0.19 in EBVaGCs and 0.96 ± 0.43 in EBVnGCs respectively. The difference between the two groups was not significant （t = 1.93, P = 0.06）. FTase β mRNA expression was not significantly different （t = 0.54, P = 0.60） between EBVaGCs and corresponding adjacent tissues either, while it was significant （t = 2.39, P = 0.02） between EBVnGCs and corresponding adjacent tissues. The level of FTase β mRNA expression had no significant relationship between 2 BHRF1 positive samples and 11 BHRF1 negetive samples of EBVaGCs （t = 0.26, P = 0.80） as well as between 6 BARF1 positive samples and 7 BARF1 negetive samples of EBVaGCs （t = 1.59, P = 0.14）. CONCLUSION： The frequency of ras gene mutations in gastric carcinomas is low in this study. The level of FTase β mRNA expression in gastric carcinomas is much higher than that in normal tissues. EBV infection has no significant correlations with ras mutations and FTase expression in EBVaGC.