胃癌组织中FHIT、Bcl-2蛋白表达与幽门螺杆菌感染的关系
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摘要
目的探讨胃癌组织中脆性组氨酸三联体(FHIT)、Bcl-2蛋白表达与幽门螺杆菌(Hp)感染的关系。方法收集2013年1月～2017年1月于解放军第四六四医院行胃癌根治术的80例胃癌组织标本,另选其中43例癌旁组织。采用快速尿素酶试纸和Warthin-Starry染色,检测组织标本是否感染Hp,采用免疫组化染色方法检测组织标本中FHIT和Bcl-2的表达。结果胃癌组织FHIT阳性表达率低于癌旁组织(P <0.05),胃癌组织Bcl-2阳性表达率高于癌旁组织(P <0.05)。胃癌组织中FHIT的表达与淋巴转移、远处转移、分化程度、浸润程度和Hp感染均有关(均P <0.05),Bcl-2的表达与肿瘤直径、分化程度、浸润程度和Hp感染有关(均P <0.05)。FHIT的阳性率与Hp感染呈负相关(r=-0.295,P <0.05),Bcl-2的阳性率与Hp感染呈正相关(r=0.393,P <0.05)。结论胃癌组织中FHIT蛋白表达减弱,Bcl-2蛋白表达增强,且均与Hp感染关系密切,三者相互作用导致了胃癌的发生。
Objective To investigate the relationship between fragile histidine triad(FHIT) and Bcl-2 protein expression in gastric cancer tissues and helicobacter pylori(Hp) infection. Methods From January 2013 to January 2017, 80 gastric carcinoma tissue samples were collected after radical gastrectomy in the 464 th Hospital of PLA, and 43 paracancerous tissues were selected. Rapid urease assay paper and Warthin-Starry staining were used to detect whether the tissue samples were infected with Hp, and the expressions of FHIT and Bcl-2 in the tissue samples were detected by immunohistochemical staining. Results FHIT positive expression rate in gastric carcinoma tissues was lower than that in para-carcinoma tissues(P < 0.05), Bcl-2 positive expression rate in gastric carcinoma tissues was higher than that in para-carcinoma tissues(P < 0.05). The expression of FHIT in gastric carcinoma tissues was related to lymphatic metastasis, distant metastasis, degree of differentiation, degree of infiltration and Hp infection(all P < 0.05). Bcl-2 expression was related to tumor diameter, differentiation degree, infiltration degree and Hp infection(all P < 0.05). The positive rate of FHIT was negatively correlated with Hp infection(r =-0.295, P < 0.05), and the positive rate of Bcl-2 was positively correlated with Hp infection(r = 0.393, P < 0.05). Conclusion The expression of FHIT protein in gastric carcinoma tissues is weakened, and the expression of Bcl-2 protein is enhanced, which are closely related to Hp infection, and the three interactions lead to the occurrence of gastric carcinoma.
Objective To investigate the relationship between fragile histidine triad(FHIT) and Bcl-2 protein expression in gastric cancer tissues and helicobacter pylori(Hp) infection. Methods From January 2013 to January 2017, 80 gastric carcinoma tissue samples were collected after radical gastrectomy in the 464 th Hospital of PLA, and 43 paracancerous tissues were selected. Rapid urease assay paper and Warthin-Starry staining were used to detect whether the tissue samples were infected with Hp, and the expressions of FHIT and Bcl-2 in the tissue samples were detected by immunohistochemical staining. Results FHIT positive expression rate in gastric carcinoma tissues was lower than that in para-carcinoma tissues(P < 0.05), Bcl-2 positive expression rate in gastric carcinoma tissues was higher than that in para-carcinoma tissues(P < 0.05). The expression of FHIT in gastric carcinoma tissues was related to lymphatic metastasis, distant metastasis, degree of differentiation, degree of infiltration and Hp infection(all P < 0.05). Bcl-2 expression was related to tumor diameter, differentiation degree, infiltration degree and Hp infection(all P < 0.05). The positive rate of FHIT was negatively correlated with Hp infection(r =-0.295, P < 0.05), and the positive rate of Bcl-2 was positively correlated with Hp infection(r = 0.393, P < 0.05). Conclusion The expression of FHIT protein in gastric carcinoma tissues is weakened, and the expression of Bcl-2 protein is enhanced, which are closely related to Hp infection, and the three interactions lead to the occurrence of gastric carcinoma.
引文
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[8]王霞.内镜活检胃癌组织中HER-2蛋白表达及临床意义[J].现代消化及介入诊疗,2017,22(3):307-310.
[9]孙燕,刘南植.幽门螺杆菌致胃上皮细胞凋亡的机制及其在胃癌发生中的作用[J].国际内科学杂志,2004,31(10):419-421.
[10]苑博,李建功,成雨.螺旋杆菌与胆管癌的关系[J].临床肝胆病杂志,2018,34(2):444-447.
[11]Watanabe T,Tada M,Nagai H,et al.Helicobacter pylori infection induces gastric cancer in mongolian gerbils[J].Gastroenterology,1998,115(3):642-648.
[12]Hu B,Wang H,Wang X,et al.Fhit and CHK1 have opposing effects on homologous recombination repair[J].Cancer Res,2005,65(19):8613.
[13]Pekarsky Y,Zanesi N,Palamarchuk A,et al.FHIT:from gene discovery to cancer treatment and prevention[J].Lancet Oncol,2002,3(12):748-754.
[14]Barnes LD,Garrison PN,Siprashvili Z,et al.Fhit,a putative tumor suppressor in humans,is a dinucleoside 5′,5"′-P1,P3-triphosphate hydrolase[J].Biochemistry,1996,35(36):11529-11535.
[15]Baffa R,Veronese ML,Santoro R,et al.Loss of FHIT expression in gastric carcinoma[J].Cancer Res,1998,58(20):4708.
[16]Huiping C,Kristjansdottir S,Bergthorsson JT,et al.High frequency of LOH,MSI and abnormal expression of FHITin gastric cancer[J].Eur J Cancer,2002,38(5):728-735.
[17]Rocco A,Schandl LJ,Wang H,et al.Loss of FHIT protein expression correlates with disease progression and poor differentiation in gastric cancer[J].J Cancer Res Clin Oncol,2003,129(2):84-88.
[18]Zhang H,Fang DC,Wang RQ,et al.Effect of Helicobacter pylori infection on expression of Bcl-2 family members in gastric adenocarcinoma[J].World J Gastroenterol,2004,10(2):227-230.
[19]Lam M,Dubyak G,Chen L,et al.Evidence that BCL-2represses apoptosis by regulating endoplasmic reticulumassociated Ca2+fluxes[J].Proc Natl Acad Sci U S A,1994,91(14):6569-6573.
[20]Hockenbery DM,Oltvai ZN,Yin XM,et al.Bcl-2 functions in an antioxidant pathway to prevent apoptosis[J].Cell,1993,75(2):241-251.
[21]Korsmeyer SJ.BCL-2 gene family and the regulation of programmed cell death[J].Cancer Res,1994,59(3):387.
[22]刘海峰,刘为纹,房殿春,等.bcl-2蛋白在胃癌组织中的表达和意义[J].肿瘤防治研究,1997,24(5):269-271.
[23]Jr BW,Martini MR,Squassoni AC,et al.Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in patients with chronic gastritis and gastric cancer[J].Dig Dis Sci,2010,55(1):111-116.
[2]徐飚,王建明.胃癌流行病学研究[J].中华肿瘤防治杂志,2006,13(1):1-7.
[3]秦叔逵,龚新雷.晚期胃癌化疗的现状和新进展[J].临床肿瘤学杂志,2006,11(9):641-652.
[4]Ohta M,Inoue H,Cotticelli MG,et al.The FHIT gene,spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8)breakpoint,is abnormal in digestive tract cancers[J].Cell,1996,84(4):587-597.
[5]杨健,胡宏波,贾安平,等.FHIT基因在胃癌中的甲基化表达及其与胃癌临床病理特征的关系[J].海南医学,2011,22(10):41-43.
[6]刘改芳,林三仁.幽门螺杆菌感染与胃癌关系的研究进展[J].中国实用内科杂志,2003,23(9):573-574.
[7]杨勇,田敏.胃镜活检病理对胃癌诊断价值分析[J].现代消化及介入诊疗,2017,22(5):653-654.
[8]王霞.内镜活检胃癌组织中HER-2蛋白表达及临床意义[J].现代消化及介入诊疗,2017,22(3):307-310.
[9]孙燕,刘南植.幽门螺杆菌致胃上皮细胞凋亡的机制及其在胃癌发生中的作用[J].国际内科学杂志,2004,31(10):419-421.
[10]苑博,李建功,成雨.螺旋杆菌与胆管癌的关系[J].临床肝胆病杂志,2018,34(2):444-447.
[11]Watanabe T,Tada M,Nagai H,et al.Helicobacter pylori infection induces gastric cancer in mongolian gerbils[J].Gastroenterology,1998,115(3):642-648.
[12]Hu B,Wang H,Wang X,et al.Fhit and CHK1 have opposing effects on homologous recombination repair[J].Cancer Res,2005,65(19):8613.
[13]Pekarsky Y,Zanesi N,Palamarchuk A,et al.FHIT:from gene discovery to cancer treatment and prevention[J].Lancet Oncol,2002,3(12):748-754.
[14]Barnes LD,Garrison PN,Siprashvili Z,et al.Fhit,a putative tumor suppressor in humans,is a dinucleoside 5′,5"′-P1,P3-triphosphate hydrolase[J].Biochemistry,1996,35(36):11529-11535.
[15]Baffa R,Veronese ML,Santoro R,et al.Loss of FHIT expression in gastric carcinoma[J].Cancer Res,1998,58(20):4708.
[16]Huiping C,Kristjansdottir S,Bergthorsson JT,et al.High frequency of LOH,MSI and abnormal expression of FHITin gastric cancer[J].Eur J Cancer,2002,38(5):728-735.
[17]Rocco A,Schandl LJ,Wang H,et al.Loss of FHIT protein expression correlates with disease progression and poor differentiation in gastric cancer[J].J Cancer Res Clin Oncol,2003,129(2):84-88.
[18]Zhang H,Fang DC,Wang RQ,et al.Effect of Helicobacter pylori infection on expression of Bcl-2 family members in gastric adenocarcinoma[J].World J Gastroenterol,2004,10(2):227-230.
[19]Lam M,Dubyak G,Chen L,et al.Evidence that BCL-2represses apoptosis by regulating endoplasmic reticulumassociated Ca2+fluxes[J].Proc Natl Acad Sci U S A,1994,91(14):6569-6573.
[20]Hockenbery DM,Oltvai ZN,Yin XM,et al.Bcl-2 functions in an antioxidant pathway to prevent apoptosis[J].Cell,1993,75(2):241-251.
[21]Korsmeyer SJ.BCL-2 gene family and the regulation of programmed cell death[J].Cancer Res,1994,59(3):387.
[22]刘海峰,刘为纹,房殿春,等.bcl-2蛋白在胃癌组织中的表达和意义[J].肿瘤防治研究,1997,24(5):269-271.
[23]Jr BW,Martini MR,Squassoni AC,et al.Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in patients with chronic gastritis and gastric cancer[J].Dig Dis Sci,2010,55(1):111-116.