TISSUE METABOLOMIC PROFILE IN OCCULT HBV INFECTION-RELATED HEPATOCELLULAR CARCINOMA,USING HIGH-RESOLUTION MAGIC-ANGLE SPINNING 1H NMR SPECTROSCOPY

【作者】 岑超； 俞军； 余松峰； 刘纪民； 刘原兴； 叶于富； 张维晨； 周琳； 谢海洋； 郑树森；

【Author】 Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital,School of Medicine,Zhejiang University;Key Laboratory of Combined Multi-organ Transplantation,Ministry of Public Health,Key Laboratory of Organ Transplantation;Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases;Department of Pathology and Molecular Medicine,Faculty of Health Sciences,McMaster University;

【机构】 Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital,School of Medicine,Zhejiang University； Key Laboratory of Combined Multi-organ Transplantation,Ministry of Public Health,Key Laboratory of Organ Transplantation； Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases； Department of Pathology and Molecular Medicine,Faculty of Health Sciences,McMaster University；

【摘要】 Aim:Hepatitis B virus (HBV) represents a major risk factor for the development of hepatocellular carcinoma(HCC).Occult HBV infection,reflected by hepatitis B surface antigen negative/hepatitis B core antibody positive(HBsAg-/anti-HBc+),is highly prevalent in HCC patient and may play an important role in hepatocarcinogenesis through the expression of oncogenic viral protein.In this study,we aimed to investigate the metabolomic signatures of occult HBV infection-related HCC,to further understand the pathogenesis of this disease.ii) Methods:Tumor and adjacent non-tumor tissues from 30 HBsAg+/anti-HBc+HCC patients and 30 HBsAg-/anti-HBc+HCC patients were analyzed,using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy.Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) was performed to compare the expression of metabolomic profiles.iii) Results:Metabolic profile was identified in tissues from all four groups.The level of expression varied between tumor and non-tumor tissues in both HBsAg+/anti-HBc+and HBsAg-/anti-HBc+groups,with high sensitivity and specificity (AUC=0.997,0.975 respectively).Additionally,the contents of hypoxanthine,histidine,phenylalanine,tryptophan were higher in HBsAg+/anti-HBc+HCC tissues,comparing to HBsAg-/anti-HBc+HCC tissues (R2X=0.206,Q2=0.362,P=7.0689X10-5),indicating upregulation of protein turnover and nucleotide biosynthesis.iv) Conclusion:In HCC patients,the tissue metabolomic profile expressed differently between HBsAg+/anti-HBc+and HBsAg-/anti-HBc+groups.The novel findings may enlighten our understanding of the pathogenesis of occult HBV infection-related HCC and lead to the further development of appropriate molecular targeted therapy.更多还原

【Abstract】 Aim:Hepatitis B virus (HBV) represents a major risk factor for the development of hepatocellular carcinoma(HCC).Occult HBV infection,reflected by hepatitis B surface antigen negative/hepatitis B core antibody positive(HBsAg-/anti-HBc+),is highly prevalent in HCC patient and may play an important role in hepatocarcinogenesis through the expression of oncogenic viral protein.In this study,we aimed to investigate the metabolomic signatures of occult HBV infection-related HCC,to further understand the pathogenesis of this disease.ii) Methods:Tumor and adjacent non-tumor tissues from 30 HBsAg+/anti-HBc+HCC patients and 30 HBsAg-/anti-HBc+HCC patients were analyzed,using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy.Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) was performed to compare the expression of metabolomic profiles.iii) Results:Metabolic profile was identified in tissues from all four groups.The level of expression varied between tumor and non-tumor tissues in both HBsAg+/anti-HBc+and HBsAg-/anti-HBc+groups,with high sensitivity and specificity (AUC=0.997,0.975 respectively).Additionally,the contents of hypoxanthine,histidine,phenylalanine,tryptophan were higher in HBsAg+/anti-HBc+HCC tissues,comparing to HBsAg-/anti-HBc+HCC tissues (R2X=0.206,Q2=0.362,P=7.0689X10-5),indicating upregulation of protein turnover and nucleotide biosynthesis.iv) Conclusion:In HCC patients,the tissue metabolomic profile expressed differently between HBsAg+/anti-HBc+and HBsAg-/anti-HBc+groups.The novel findings may enlighten our understanding of the pathogenesis of occult HBV infection-related HCC and lead to the further development of appropriate molecular targeted therapy.更多还原