胃癌相关甲基化分型与幽门螺杆菌感染的探讨

目的 探讨基因甲基化分型与幽门螺杆菌感染在胃癌预后中的临床价值。方法 使用甲基化特异性PCR技术分析75例胃癌病人血清中的CpG岛甲基化分型(CIMP),同时分析了40例健康人血清作为对照。APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK和E-cad作为研究基因。幽门螺杆菌感染由血清抗幽门螺杆菌G抗体试验和快速脲酶试验确定。结果 7个基因胃癌组织中甲基化的频率如下:APC 48%,WIF-1 57.33%,RUNX-3 56%,DLC-1 50.67%,SFRP-1 52%,DKK54.67%和E-cad 48%; 血清中甲基化的频率如下:APC 30.67%,WIF-1 34.67%,RUNX-3 37.33%,DLC-1 29.33%,SFRP-1 33.33%,DKK 32%和E-cad 26.67%。CIMP+(定义为≥3甲基化基因)与47例(62.67%)胃癌组织标本和44例(58.67%)GC血清样品相关联。CIMP+与非肿瘤黏膜组织和健康人的血清无关联。在75例胃癌中,有51例(68%)为幽门螺杆菌阳性,24例(32%)为幽门螺杆菌阴性。在51例幽门螺杆菌感染胃癌组织中,36例为CIMP+,15例为CIMP-。相反,在24例幽门螺杆菌阴性病例中,11例为CIMP+,13例为CIMP-。两组CIMP表达差异有统计学意义(χ2=4.27,P<0.05)。在51例幽门螺杆菌阳性胃癌血清样本中,34例为CIMP+,17例为CIMP-。24例未感染血清样本中,10例CIMP+,14例CIMP-。两组间差异有统计学意义(χ2= 4.21,P<0.05)。经过两年随访,发现HP+/CIMP+和HP+/CIMP-两组转移、复发率明显不同,HP+/CIMP+病人有转移、复发倾向(P<0.05); 生存率二者未见明显不同(P>0.05)。结论 HP+/CIMP+的病人比HP+/CIMP-更易转移和复发。

Relationship between the CpG Island Methylator Phenotypeand Helicobacter Pylori Infection Associated with Gastric Cancer

Objective To investigate the association between the CpG island methylator penotype(CIMP)and serum Helicobacter pylori(H.pylori)levels for clinical prediction of gastric cancer(GC)progression.Methods Analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction.Serum samples from 40 healthy persons were examined at the same time.The genes examined were APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad respectively.H.pylori infection in serum was assayed with an anti-H.pylori immunoglobulin G antibody test and a rapid urease test.Results The frequencies of high-level methylation in GC tissues for the seven geneswere:48% for APC,57.33% for WIF-1,56% for RUNX-3,50.67% for DLC-1,52%for SFRP-1,54.67% for DKK,and 48% for E-cad.The frequencies in GC serum were 30.67% for APC,34.67% for WIF-1,37.33% for RUNX-3,29.33% for DLC-1,33.33% for SFRP-1,32% for DKK,and 26.67% for E-cad.CIMP+(defined as≥3methylated genes)was associated with 47(62.67%)GC tissue samples and 44(58.67%)GC serum samples.CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons.Of the 75 GC cases,51(68%)were H.pylori+,and 24(32%)were H.pylori-.Of the 51 H.pylori+ cases,36 were CIMP+ and 15 were CIMP-.In contrast,for the 24 H.pylori- cases,11 were CIMP+,and 13 were CIMP-.The difference was significant between the H.pylori+ and H.pylori- groups(χ2=4.27,P<0.05).Of the 51 H.pylori+ GC patients,34 were CIMP+ and 17 were CIMP-,while among the 24 H.pylori- GC cases,10 were CIMP+ and 14 were CIMP-.The difference was significantbetween the H.pylori+ and H.pylori- groups(χ2=4.21,P< 0.05).A 2-year follow- up showed significant difference in the rates of metastasisand recurrence between H.pylori+/CIMP+ cases and the H.pylori+/CIMP- cases or CIMP- cases associated with H.pylori assayed in serum(P<0.05).However,there were no significant differences in survival rates between thetwo groups.Conclusion H.pylori+/CIMP+ cases were associated with higher rates of metastasis and recurrence than H.pylori+/CIMP- cases.Serum may be useful for examining CIMP status.