慢性萎缩性胃炎胃黏膜Runx3基因及蛋白表达与幽门螺杆菌感染的关系研究
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摘要
目的探讨幽门螺杆菌(Hp)感染对慢性萎缩性胃炎(CAG)患者胃黏膜Runx3表达的影响,以及根除Hp后CAG患者胃黏膜Runx3表达的变化。方法选取2016年1月至2017年6月确诊的CAG患者80例,其中53例Hp阳性者为观察组,27例Hp阴性者为对照组,比较两组患者Runx3mRNA和蛋白表达水平。观察组所有患者进行根除Hp治疗,比较根除Hp前后患者胃黏膜Runx3mRNA和蛋白表达的变化。结果观察组CAG患者胃黏膜Runx3基因甲基化阳性率(52.8%)高于对照组(29.6%),差异有统计学意义(χ2=3.890,P=0.049)。观察组患者胃黏膜Runx3mRNA表达水平(0.82±0.22)低于对照组(0.89±0.28),差异无统计学意义(P=0.221);观察组患者Runx3蛋白的表达水平(0.38±0.22)低于对照组(0.50±0.24),差异有统计学意义(t=1.233,P=0.035)。观察组53例患者根除Hp治疗后44例Hp转阴,根除Hp后患者胃黏膜Runx3mRNA及蛋白(0.88±0.22、0.42±0.21)表达较根除前(0.83±0.23、0.38±0.22)升高,差异均有统计学意义(t=-3.249、-3.166,P=0.002、0.003)。结论 Hp感染可降低CAG患者胃黏膜Runx3mRNA和蛋白的表达,根除Hp后CAG患者胃黏膜Runx3mRNA及蛋白表达上调。
Objective To explore the effect of Helicobacter pylori(Hp)infection on Runx3 expression in gastric mucosa of patients with chronic atrophic gastritis(CAG),and observe changes of Runx3 expression in gastric mucosa of patients with CAG after Hp eradication therapy.Methods A total of 80 patients diagnosed with CAG from January 2016 to June 2017 were selected,and were divided into the observation group(53 cases with Hp infection)and the control group(27 cases without Hp infection).The Runx3 mRNA and protein expressions of the two groups were compared.All patients in the observation group received Hp eradication therapy,and the expression levels of Runx3 mRNA and protein before and after Hp eradication therapy were compared.Results The positive rate of Runx3 gene methylation in gastric mucosa in the observation group(52.8%)was higher than that of the control group(29.6%),there was statistically significant difference(χ2=3.890,P=0.049).The Runx3 mRNA expression level in gastric mucosa in the observation group(0.82±0.22)was lower than that in the control group(0.89±0.28),there was no statistically significant difference(P=0.221);the Runx3 protein expression in gastric mucosa in the observation group(0.38±0.22)was also lower than that in the control group(0.50±0.24),there was statistically significant difference(t=1.233,P=0.035).After Hp eradication therapy 44 of 53 cases in the observation group turned to Hp-negative.The Runx3 mRNA and protein expression levels of patients in the observation group after Hp eradication were significantly increased compared with before Hp eradication therapy(P<0.05).Conclusion Hp infection can reduce the Runx3 mRNA and protein expression in gastric mucosa of patients with CAG,and the expression levels are up-regulated after Hp eradication.
Objective To explore the effect of Helicobacter pylori(Hp)infection on Runx3 expression in gastric mucosa of patients with chronic atrophic gastritis(CAG),and observe changes of Runx3 expression in gastric mucosa of patients with CAG after Hp eradication therapy.Methods A total of 80 patients diagnosed with CAG from January 2016 to June 2017 were selected,and were divided into the observation group(53 cases with Hp infection)and the control group(27 cases without Hp infection).The Runx3 mRNA and protein expressions of the two groups were compared.All patients in the observation group received Hp eradication therapy,and the expression levels of Runx3 mRNA and protein before and after Hp eradication therapy were compared.Results The positive rate of Runx3 gene methylation in gastric mucosa in the observation group(52.8%)was higher than that of the control group(29.6%),there was statistically significant difference(χ2=3.890,P=0.049).The Runx3 mRNA expression level in gastric mucosa in the observation group(0.82±0.22)was lower than that in the control group(0.89±0.28),there was no statistically significant difference(P=0.221);the Runx3 protein expression in gastric mucosa in the observation group(0.38±0.22)was also lower than that in the control group(0.50±0.24),there was statistically significant difference(t=1.233,P=0.035).After Hp eradication therapy 44 of 53 cases in the observation group turned to Hp-negative.The Runx3 mRNA and protein expression levels of patients in the observation group after Hp eradication were significantly increased compared with before Hp eradication therapy(P<0.05).Conclusion Hp infection can reduce the Runx3 mRNA and protein expression in gastric mucosa of patients with CAG,and the expression levels are up-regulated after Hp eradication.
引文
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[14]NOMURA A,GROVE J S,STEMMEMANN G N,et al.A prospective study of stomach cancer and its relation to diet,cigarettes,and alcohol consumption[J].Cancer Res,1990,50(3):627-631.
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[16]ZHANG X,HE H,ZHANG X,et al.RUNX3promoter methylation is associated with hepatocellular carcinoma risk:A meta-analysis[J].Cancer Invest,2015,33(4):121-125.
[17]LOTEM J,LEVANON D,NEGREANU V,et al.Runx3at the interface of immunity,inflammation and cancer[J].Biochim Biophys Acta,2015,1855(2):131-143.
[18]BANGSOW C,RUBINS N,GLUSMAN G,et al.The RUNX3gene-sequence,structure and regulated expression[J].Gene,2001,279(2):221-232.
[19]LI Q L,ITO K,SAKAKURA C,et al.Causal relationship between the loss of RUNX3expression and gastric cancer[J].Cell,2002,109(1):113-124.
[20]BARUTCU A R,HONG D,LAJOIE B R,et al.RUNX1contributes to higher-order chromatin organization and gene regulation in breast cancer cells[J].Biochim Biophys Acta,2016(16):30170-30175.
[21]LIU G,XIANG T,WU Q F,et al.Long noncoding RNA H19-derived miR-675enhances proliferation and invasion via RUNX1in gastric cancer cells[J].Oncol Res,2016,23(3):99-107.
[22]黄唯,李啸峰,王安,等.胃癌前病变中H.ylori感染下调RUNx的表达[J].岭南急诊医学杂志,2010,15(1):15-17.
[23]赵春娜,肖丽丽,王倍,等.慢性萎缩性胃炎患者Runx3基因甲基化水平的研究[J].胃肠病学,2016,21(8):470-473.
[24]KANG C,SONG J J,LEE J,et al.Epigenetics:an emerging player in gastric cancer[J].World J Gastroenterol,2014,20(21):6433-6447.
[25]PATEL T N,ROY S,RAVI R.Gastric cancer and related epigenetic alterations[J].E Cancer Med Sci,2017,17(11):714.
[26]CHOI J,KIM S G,KIM B G,et al.Helicobacter pylori eradication modulates aberrant CpG island hypermethylation in gastric carcinogenesis[J].Korean J Gastroenterol,2016,68(5):253-259.
[2] FERLARY J,SOERJOMATARAM I,DIKSHIT R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].Int J Cancer,2015,136(5):E359-E386.
[3] CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA,2016,66(2):115-132.
[4]中华医学会消化病学分会.中国慢性胃炎共识意见(2017年,上海)[J].胃肠病学,2017,22(11):670-687.
[5]廖莉莉,杨百京.中西医结合治疗慢性萎缩性胃炎合并幽门螺杆菌感染的临床疗效观察[J].重庆医学,2017,46(29):4164-4165.
[6] ZHAO C,LI P,ZHANG L,et al.An observational study on aberrant methylation of Runx3with the prognosis in chronic atrophic gastritis patients[J].Medicine(Baltimore),2016,95(20):e3356.
[7]刘文忠,谢勇,成虹,等.第四次全国幽门螺杆菌感染处理共识报告[J].胃肠病学,2012,17(10):618-625.
[8] SONG H,HELD M,SANDIN S,et al.Increase in the prevalence of atrophic gastritis among adults age 35to 44years old in Northern Sweden between 1990and 2009[J].Clin Gastroenterol Hepatol,2015,13(9):1592-1600.
[9] HULLAR M A,FU B C.Diet,the gut microbiome,and epigenetics[J].Cancer J,2014,20(3):170-175.
[10]BORNSHEIN J,MALFERTHEINER P.Helicobacter pylori and gastric cancer[J].Dig Dis,2014,32(3):249-264.
[11]JIA Z F,ZHANG S I,CAO X Y,et al.Interaction between Helicobacter pylori and host genetic variants in gastric carcinogenesis[J].Future Oncol,2016,12(18):2127-2134.
[12]HONG J B,ZUO W,WANG A J,et al.Helicobacter pylori infection synergistic with IL-1beta gene polymorphisms potentially contributes to the carcino-genesis of gastric cancer[J].Int J Med Sci,2016,13(4):298-303.
[13]CHOOI E Y,CHEN H M,SHEN L,et al.Chronic atrophy gastritis is a progressive disease:analysis of medical reports from Shanghai(1985-2009)[J].Singapore Med J,2012,53(5):318-324.
[14]NOMURA A,GROVE J S,STEMMEMANN G N,et al.A prospective study of stomach cancer and its relation to diet,cigarettes,and alcohol consumption[J].Cancer Res,1990,50(3):627-631.
[15]GAO Q Y,WANG Z H,CHOOI E Y,et al.A novel model might predict the risk of chronic atrophic gastritis:a multicenter rospective study in China[J].Scand J Gastroenterol,2012,47(5):509-517.
[16]ZHANG X,HE H,ZHANG X,et al.RUNX3promoter methylation is associated with hepatocellular carcinoma risk:A meta-analysis[J].Cancer Invest,2015,33(4):121-125.
[17]LOTEM J,LEVANON D,NEGREANU V,et al.Runx3at the interface of immunity,inflammation and cancer[J].Biochim Biophys Acta,2015,1855(2):131-143.
[18]BANGSOW C,RUBINS N,GLUSMAN G,et al.The RUNX3gene-sequence,structure and regulated expression[J].Gene,2001,279(2):221-232.
[19]LI Q L,ITO K,SAKAKURA C,et al.Causal relationship between the loss of RUNX3expression and gastric cancer[J].Cell,2002,109(1):113-124.
[20]BARUTCU A R,HONG D,LAJOIE B R,et al.RUNX1contributes to higher-order chromatin organization and gene regulation in breast cancer cells[J].Biochim Biophys Acta,2016(16):30170-30175.
[21]LIU G,XIANG T,WU Q F,et al.Long noncoding RNA H19-derived miR-675enhances proliferation and invasion via RUNX1in gastric cancer cells[J].Oncol Res,2016,23(3):99-107.
[22]黄唯,李啸峰,王安,等.胃癌前病变中H.ylori感染下调RUNx的表达[J].岭南急诊医学杂志,2010,15(1):15-17.
[23]赵春娜,肖丽丽,王倍,等.慢性萎缩性胃炎患者Runx3基因甲基化水平的研究[J].胃肠病学,2016,21(8):470-473.
[24]KANG C,SONG J J,LEE J,et al.Epigenetics:an emerging player in gastric cancer[J].World J Gastroenterol,2014,20(21):6433-6447.
[25]PATEL T N,ROY S,RAVI R.Gastric cancer and related epigenetic alterations[J].E Cancer Med Sci,2017,17(11):714.
[26]CHOI J,KIM S G,KIM B G,et al.Helicobacter pylori eradication modulates aberrant CpG island hypermethylation in gastric carcinogenesis[J].Korean J Gastroenterol,2016,68(5):253-259.