hABH2参与幽门螺旋杆菌致胃癌发生机制的相关研究
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摘要
目的探讨hABH2基因是否参与幽门螺旋杆菌(Hp)感染致胃癌发生机制过程。方法收集2016年1月至2017年12月间在松江区中心医院内镜室行胃镜检查的Hp (+)/(-)慢性胃炎组织60例及胃癌组织30例,根据患者1·3·C呼气试验结果,将其分为慢性胃炎Hp (-)组、慢性胃炎Hp (+)组、胃癌Hp (-)组和胃癌Hp (+)组。以实时定量PCR法和免疫组化法检测各例中hABH2基因及蛋白水平的表达情况。结果与慢性胃炎组相比,胃癌组患者的hABH2基因[(0.915±0.181) vs (1.532±0.185)]和蛋白[(2.628±0.296) vs (6.273±0.445)]表达水平均显著降低,差异均有统计学意义(P<0.05);慢性胃炎组内,与Hp (-)亚组(n=47)相比,Hp (+)亚组(n=13) hABH2基因[(3.456±0.257) vs(1.000±0.151)]及蛋白[(9.667±0.927) vs (5.334±0.418)]表达水平均显著升高,差异均有统计学意义(P<0.05);胃癌组内,与Hp (-)亚组(n=11)相比,Hp (+)亚组(n=19) h ABH2基因[(1.116±0.340) vs (0.797±0.210)]及蛋白[(2.828±0.298) vs(2.283±0.630)]表达水平无明显变化,差异均无统计学意义(P>0.05)。结论 hABH2在感染Hp的慢性胃炎组织中表达增多,可能是由机体自身负反馈保护机制所致;hABH2可能部分参与了Hp致胃癌的发生机制。
Objective To investigate whether hABH2 gene is involved in the pathogenesis of gastric cancer caused by Helicobacter pylori(Hp) infection. Methods Sixty Hp(+)/(-) chronic gastritis tissue samples and 30 gastric cancer tissue samples were collected from the endoscopy room of Shanghai Songjiang District Central Hospital from January 2016 to December 2017. According to the patient's13 C breath test results, they were divided into chronic gastritis Hp(-) group, chronic gastritis Hp(+) group, gastric cancer Hp(-) group, gastric cancer Hp(+) group. The expression of hABH2 gene and protein in 60 patients with chronic gastritis and 30 patients with gastric cancer were detected by realtime quantitative RT-PCR and immunohistochemistry. Results Compared with chronic gastritis group, the expression of hABH2 gene and protein in gastric cancer group was significantly lower(P<0.05):(0.915±0.181) vs(1.532±0.185),(2.628 ± 0.296) vs(6.273 ± 0.445). In chronic gastrisis group, compared with Hp(-) group(n=47), the expression of hABH2 gene and protein in Hp(+) group(n=13) was significantly higher(P<0.05):(3.456±0.257) vs(1.000±0.151),(9.667±0.927) vs(5.334±0.418). In gastric cancer, there was no significant difference in hABH2 gene and protein expression between Hp(-) group and Hp(+) group(P>0.05):(1.116±0.340) vs(0.797±0.210),(2.828±0.298) vs(2.283±0.630).Conclusion The expression of h ABH2 in chronic gastritis infected with Hp may be caused by the existence of negative feedback protection mechanism in the body itself. It is speculated that hABH2 may partially participate in the pathogenesis of Hp-induced gastric cancer.
Objective To investigate whether hABH2 gene is involved in the pathogenesis of gastric cancer caused by Helicobacter pylori(Hp) infection. Methods Sixty Hp(+)/(-) chronic gastritis tissue samples and 30 gastric cancer tissue samples were collected from the endoscopy room of Shanghai Songjiang District Central Hospital from January 2016 to December 2017. According to the patient's13 C breath test results, they were divided into chronic gastritis Hp(-) group, chronic gastritis Hp(+) group, gastric cancer Hp(-) group, gastric cancer Hp(+) group. The expression of hABH2 gene and protein in 60 patients with chronic gastritis and 30 patients with gastric cancer were detected by realtime quantitative RT-PCR and immunohistochemistry. Results Compared with chronic gastritis group, the expression of hABH2 gene and protein in gastric cancer group was significantly lower(P<0.05):(0.915±0.181) vs(1.532±0.185),(2.628 ± 0.296) vs(6.273 ± 0.445). In chronic gastrisis group, compared with Hp(-) group(n=47), the expression of hABH2 gene and protein in Hp(+) group(n=13) was significantly higher(P<0.05):(3.456±0.257) vs(1.000±0.151),(9.667±0.927) vs(5.334±0.418). In gastric cancer, there was no significant difference in hABH2 gene and protein expression between Hp(-) group and Hp(+) group(P>0.05):(1.116±0.340) vs(0.797±0.210),(2.828±0.298) vs(2.283±0.630).Conclusion The expression of h ABH2 in chronic gastritis infected with Hp may be caused by the existence of negative feedback protection mechanism in the body itself. It is speculated that hABH2 may partially participate in the pathogenesis of Hp-induced gastric cancer.
引文
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[23]TREWICK SC,HENSHAW TF,HAUSINGER RP,et al.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J].Nature,2002,419(6903):174-178.
[2]王凯娟,王润田.中国幽门螺杆菌感染流行病学Meta分析[J].中华流行病学杂志,2003,24(6):443-446.
[3]BUTCHER LD,DEN HARTOG G,ERNST PB,et al.Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis[J].Cell Mol Gastroenterol Hepatol,2017,3(3):316-322.
[4]MISHINA Y,HE C.Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins[J].J Inorg Biochem,2006,100(4):670-678.
[5]SAKUMA K,CHONG JM,SUDO M,et al.High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma[J].Int J Cancer,2004,112(2):273-278.
[6]KITAJIMA Y,OHTAKA K,MITSUNO M,et al.Helicobacter pylori infection is an independent risk factor for Runx3 methylation in gastric cancer[J].Oncol Rep,2008,19(1):197-202.
[7]CHAN AO,CHU KM,HUANG C,et al.Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer[J].Gut,2007,56(4):595-597.
[8]MAEKITA T,NAKAZAWA K,MIHARA M,et al.High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk[J].Clin Cancer Res,2006,12(3 Pt 1):989-995.
[9]LEVINE RL,YANG IY,HOSSAIN M,et al.Mutagenesis induced by a single 1,N6-ethenodeoxyadenosine adduct in human cells[J].Cancer Res,2000,60(15):4098-4104.
[10]NAIR U,BARTSCH H,NAIR J.Lipid peroxidation-induced DNAdamage in cancer-prone inflammatory diseases:a review of published adduct types and levels in humans[J].Free Radic Biol Med,2007,43(8):1109-1120.
[11]陈胜良,李雷佳,童菊芳,等.alkB基因在胃癌和萎缩性胃炎黏膜组织中的表达改变[J].胃肠病学,2007,12(7):401-404.
[12]AAS PA,OTTERLEI M,FALNES PO,et al.Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA[J].Nature,2003,421(6925):859-863.
[13]LEE DH,JIN SG,CAI S,et al.Repair of methylation damage in DNA and RNA by mammalian AlkB homologues[J].J Biol Chem,2005,280(47):39448-39459.
[14]KUROWSKI MA,BHAGWAT AS,PAPAJ G,et al.Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB[J].BMC Genomics,2003,4(1):48.
[15]GAO W,LI L,XU P,et al.Frequent down-regulation of hABH2 in gastric cancer and its involvement in growth of cancer cells[J].JGastroenterol Hepatol,2011,26(3):577-584.
[16]WANG C,YUAN Y,HUNT RH.The association between Helicobacter pylori infection and early gastric cancer:a meta-analysis[J].Am J Gastroenterol,2007,102(8):1789-1798.
[17]HUANG JQ,ZHENG GF,SUMANAC K,et al.Meta-analysis of the relationship between cagA seropositivity and gastric cancer[J].Gastroenterology,2003,125(6):1636-1644.
[18]PARK JY,FORMAN D,GREENBERG ER,et al.Helicobacter pylori eradication in the prevention of gastric cancer:are more trials needed?[J].Curr Oncol Rep,2013,15(6):517-525.
[19]OGURA K,HIRATA Y,YANAI A,et al.The effect of Helicobacter pylori eradication on reducing the incidence of gastric cancer[J].J Clin Gastroenterol,2008,42(3):279-283.
[20]PANDYA GA,MORIYA M.1,N6-ethenodeoxyadenosine,a DNAadduct highly mutagenic in mammalian cells[J].Biochemistry,1996,35(35):11487-11492.
[21]KIM YI.Folate and DNA methylation:a mechanistic link between folate deficiency and colorectal cancer[J].Cancer Epidemiol Biomarkers Prev,2004,13(4):511-519.
[22]AAS PA,OTTERLEI M,FALNES PO,et al.Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA[J].Nature,2003,421(6925):859-863.
[23]TREWICK SC,HENSHAW TF,HAUSINGER RP,et al.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J].Nature,2002,419(6903):174-178.