肝螺杆菌感染与人类原发性肝细胞癌的相关性研究
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摘要
目的本研究旨在了解肝肠源性螺杆菌是否存在于肝细胞癌患者的胆汁内,探讨此菌与肝癌的相关性。方法收集经病理确诊的47例原发性肝细胞癌患者及24例结肠直肠癌肝转移患者的胆汁标本。使用特定16SrRNA引物的聚合酶链式反应(PCR)及DNA测序检测胆汁标本中的螺杆菌属及肝螺杆菌特异性16SrRNA,并使用酶联免疫吸附法(ELISA)检测胆汁标本中的肝螺杆菌抗体。结果 47例原发性肝细胞癌患者胆汁标本中有12例(25.5%)检测出肝螺杆菌特异性16SrRNA,15例(31.9%)检测出抗肝螺杆菌抗体;24例结肠直肠癌肝转移患者胆汁标本中只有1例(4.2%)检测出肝螺杆菌特异性16SrRNA基因,3例(12.5%)检测出抗肝螺杆菌抗体(P<0.05)。结论原发性肝细胞癌患者可检测出肝螺杆菌,这可能与肝细胞癌的发病机制有一定联系。
Aim Theaimofthisstudyistoinvestigatewhether H.hepaticuscanbedetectedinthebile samples of patients with primary hepatocellular carcinoma(HCC),and to investigate the relationship between H.hepaticus and HCC.Methods Bile samples were collected from 47 patients with HCC and 24 patients with hepatic metastasis from colorectal cancer diagnosed by histopathology.These samples were screened for the presence of enterohepatic Helicobacter spp.DNA was examined using polymerase chain reaction(PCR) with specific 16S rRNA primers,and sequencing.Bile samples were also examined for the presence of H.hepaticus antibody using by enzyme-linked immunosorbent assay(ELISA).Results H.hepaticus DNA was found in 12 of 47(25.5%) bile samples from patients with HCC,and in 1 of 24(4.2%) samples from patients with liver metastatic tumor(P < 0.05).Anti-H.hepaticus antibody was found in 15 of 47(31.9%) bile samples from patients with HCC,and in 3 of 24(12.5%) samples from patients with liver metastasis(P < 0.05).Conclusion H.hepaticus infection might play an important role in the development of primary hepatocellular carcinoma.
Aim Theaimofthisstudyistoinvestigatewhether H.hepaticuscanbedetectedinthebile samples of patients with primary hepatocellular carcinoma(HCC),and to investigate the relationship between H.hepaticus and HCC.Methods Bile samples were collected from 47 patients with HCC and 24 patients with hepatic metastasis from colorectal cancer diagnosed by histopathology.These samples were screened for the presence of enterohepatic Helicobacter spp.DNA was examined using polymerase chain reaction(PCR) with specific 16S rRNA primers,and sequencing.Bile samples were also examined for the presence of H.hepaticus antibody using by enzyme-linked immunosorbent assay(ELISA).Results H.hepaticus DNA was found in 12 of 47(25.5%) bile samples from patients with HCC,and in 1 of 24(4.2%) samples from patients with liver metastatic tumor(P < 0.05).Anti-H.hepaticus antibody was found in 15 of 47(31.9%) bile samples from patients with HCC,and in 3 of 24(12.5%) samples from patients with liver metastasis(P < 0.05).Conclusion H.hepaticus infection might play an important role in the development of primary hepatocellular carcinoma.
引文
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3Fox JG,Dewhirst FE,Tully JG,et al.Helicobacter hepaticus sp.nov.,a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice.J Clin Microbiol,1994,32:12381245.
4Suerbaum S,Josenhans C,Sterzenbach T,et al.The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus.Proc Natl Acad Sci USA,2003,100:7901-7906.
5Chien CC,Taylor NS,Ge Z,et al.Identification of cdtB homologues and cytolethal distending toxin activity in enterohepatic Helicobacter spp.J Med Microbiol,2000,49:525-534.
6Parkin DM,Pisani P,Ferlay J.Estimates of the worldwide incidence of25major cancers in1990.Int J Cancer,1999,80:827-841.
7Kew MC.Epidemiology of hepatocellular carcinoma.Toxicology,2002,181-182:35-38.
8Shames B,Fox JG,Dewhirst F,et al.Identification of widespread Helicobacter hepaticus infection in feces in commercial mouse colonies by culture and PCR assay.J Clin Microbiol,1995,33:29682972.
9Fagoonee S,Pellicano R,Rizzetto M,et al.The journey from hepatitis to hepatocellular carcinoma:bridging role of Helicobacter species.Panminerva Med,2001,43:279-282.
10Sherlock S,Dooley J.Diseases of the liver and biliary system.10th Edition.Oxford:Blackwell Scientific Publications,1997.
11Huang Y,Fan XG,Wang ZM,et al.Identification of helicobacterspecies in human liver samples from patients with primary hepatocellular carcinoma.J Clin Pathol,2004,57:1273-1277.
12Pellicano R,Mazzaferro V,Grigioni WF,et al.Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma.World J Gastroenterol,2004,10:598-601.
13Nilsson I,Kornilovs′ka I,Lindgren S,et al.Increased prevalence of seropositivity for non-gastric Helicobacter species in patients with autoimmune liver disease.J Med Microbiol,2003,52(Pt11):949953.
14Fox JG,Feng Y,Theve EJ,et al.Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.Gut,2010,59:88-97.
15Avenaud P,Le Bail B,Mayo K,et al.Natural history of Helicobacter hepaticus infection in conventional A/J mice,with special reference to liver involvement.Infect lmmun,2003,71:3667-3672.
16Murakami K,Takahashi R,Ono M,et al.Serodiagnosis of Helicobacter hepaticus infection in patients with liver and gastrointestinal diseases:western blot analysis and ELISA using a highly specific monoclonal antibody for H.hepaticus antigen.J Gastroenterol,2011,46:1120-1126.
17Vorobjova T,Nilsson I,Terjajev S,et al.Serum antibodies to enterohepatic Helicobacter spp.in patients with chronic liver diseases and in a population with high prevalence of H.pylori infection.Dig Liver Dis,2006,38:171-176.
2Fox JG,Dewhirst FE,Shen Z,et al.Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis.Gastroenterology,1998,114:755-763.
3Fox JG,Dewhirst FE,Tully JG,et al.Helicobacter hepaticus sp.nov.,a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice.J Clin Microbiol,1994,32:12381245.
4Suerbaum S,Josenhans C,Sterzenbach T,et al.The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus.Proc Natl Acad Sci USA,2003,100:7901-7906.
5Chien CC,Taylor NS,Ge Z,et al.Identification of cdtB homologues and cytolethal distending toxin activity in enterohepatic Helicobacter spp.J Med Microbiol,2000,49:525-534.
6Parkin DM,Pisani P,Ferlay J.Estimates of the worldwide incidence of25major cancers in1990.Int J Cancer,1999,80:827-841.
7Kew MC.Epidemiology of hepatocellular carcinoma.Toxicology,2002,181-182:35-38.
8Shames B,Fox JG,Dewhirst F,et al.Identification of widespread Helicobacter hepaticus infection in feces in commercial mouse colonies by culture and PCR assay.J Clin Microbiol,1995,33:29682972.
9Fagoonee S,Pellicano R,Rizzetto M,et al.The journey from hepatitis to hepatocellular carcinoma:bridging role of Helicobacter species.Panminerva Med,2001,43:279-282.
10Sherlock S,Dooley J.Diseases of the liver and biliary system.10th Edition.Oxford:Blackwell Scientific Publications,1997.
11Huang Y,Fan XG,Wang ZM,et al.Identification of helicobacterspecies in human liver samples from patients with primary hepatocellular carcinoma.J Clin Pathol,2004,57:1273-1277.
12Pellicano R,Mazzaferro V,Grigioni WF,et al.Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma.World J Gastroenterol,2004,10:598-601.
13Nilsson I,Kornilovs′ka I,Lindgren S,et al.Increased prevalence of seropositivity for non-gastric Helicobacter species in patients with autoimmune liver disease.J Med Microbiol,2003,52(Pt11):949953.
14Fox JG,Feng Y,Theve EJ,et al.Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.Gut,2010,59:88-97.
15Avenaud P,Le Bail B,Mayo K,et al.Natural history of Helicobacter hepaticus infection in conventional A/J mice,with special reference to liver involvement.Infect lmmun,2003,71:3667-3672.
16Murakami K,Takahashi R,Ono M,et al.Serodiagnosis of Helicobacter hepaticus infection in patients with liver and gastrointestinal diseases:western blot analysis and ELISA using a highly specific monoclonal antibody for H.hepaticus antigen.J Gastroenterol,2011,46:1120-1126.
17Vorobjova T,Nilsson I,Terjajev S,et al.Serum antibodies to enterohepatic Helicobacter spp.in patients with chronic liver diseases and in a population with high prevalence of H.pylori infection.Dig Liver Dis,2006,38:171-176.