BACKGROUND Serum alanine aminotransferase(ALT) levels are often considered a marker to evaluate liver disease and its severity.AIM To investigate the association between ALT levels and all-cause and cause-specific mor...BACKGROUND Serum alanine aminotransferase(ALT) levels are often considered a marker to evaluate liver disease and its severity.AIM To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease(NAFLD).METHODS The Third National Health and Nutrition Examination Survey(NHANES-Ⅲ) from 1988 to 1994 and NHANES-Ⅲ-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal(ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model.RESULTS Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest allcause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors.CONCLUSION The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumo...Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of hepatocellular carcinoma(HCC) patients were screened by PCR and direct sequencing.All patients carried HBV with genotype C,except for one B/C heterozygote.The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro.The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified:pre-S 1 in-frame deletion involving the first start codon;pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion;and S promoter in-frame deletion(ASP).The first two types were evenly found in both tumor and non-tumor tissues.They were rarely present as dominant strains.The last two types were frequently found in the dominant strains in tumor tissues.The overall prevalence of HBV carrying ASP was 17.64%(6/34) in tumor tissues,but none were dominant in nontumor tissues.HBV carrying ASP was unable to produce S protein in vitro.Immunocytofluorescence assay showed that the ASP LHBs mutant aggregated in the cytoplasm,accumulating mainly in the ER.Transient transfection and expression of ASP mutant caused GRP78 up-regulation in vitro.Conclusions HBV S promoter deletion was found dominantly in HCC tumor tissue.The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.展开更多
Objective To identify the difference and significance of dominant types of hepatitis B virus (HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tum...Objective To identify the difference and significance of dominant types of hepatitis B virus (HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma (HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion (ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64% (6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.展开更多
文摘BACKGROUND Serum alanine aminotransferase(ALT) levels are often considered a marker to evaluate liver disease and its severity.AIM To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease(NAFLD).METHODS The Third National Health and Nutrition Examination Survey(NHANES-Ⅲ) from 1988 to 1994 and NHANES-Ⅲ-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal(ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model.RESULTS Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest allcause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors.CONCLUSION The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression, localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 m RNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion; pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)and the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma(HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion(ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64%(6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.Conclusion HBV S promoter deletion was found dominantly in HCC tumor tissue. The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases, Ministry of Science and Technolog of China(No. 2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus(HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of hepatocellular carcinoma(HCC) patients were screened by PCR and direct sequencing.All patients carried HBV with genotype C,except for one B/C heterozygote.The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro.The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified:pre-S 1 in-frame deletion involving the first start codon;pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion;and S promoter in-frame deletion(ASP).The first two types were evenly found in both tumor and non-tumor tissues.They were rarely present as dominant strains.The last two types were frequently found in the dominant strains in tumor tissues.The overall prevalence of HBV carrying ASP was 17.64%(6/34) in tumor tissues,but none were dominant in nontumor tissues.HBV carrying ASP was unable to produce S protein in vitro.Immunocytofluorescence assay showed that the ASP LHBs mutant aggregated in the cytoplasm,accumulating mainly in the ER.Transient transfection and expression of ASP mutant caused GRP78 up-regulation in vitro.Conclusions HBV S promoter deletion was found dominantly in HCC tumor tissue.The aggregation of mutant large surface proteins in the ER possibly involved in HBV-related HCC.
基金supported by grants from the National Projects on Major Infectious Diseases,Ministry of Science and Technolog of China(No.2009ZX10004-903)the Doctoral Fund of Ministry of Education of China(No.20100001110055)
文摘Objective To identify the difference and significance of dominant types of hepatitis B virus (HBV) pre-S mutation between liver tumor tissues and paired adjacent non-tumor tissues and to test if the mutations were tumor tissue specific.Methods HBV DNA isolated from 34 paired intratumoral and peritumoral tissues of Hepatocellular Carcinoma (HCC) patients were screened by PCR and direct sequencing. All patients carried HBV with genotype C, except for one B/C heterozygote. The expression,localization and excretion of LHBs mutant carrying pre-S deletions were characterized in vitro. The expression of endoplasmic reticulum(ER) GRP78 mRNA was assayed.Results Four patterns of pre-S mutations were identified: pre-S1 in-frame deletion involving the first start codon; pre-S2 in-frame deletion;pre-S2 start codon mutation with or without in-frame deletion; and S promoter in-frame deletion (ΔSP). The first two types were evenly found in both tumor and non-tumor tissues. They were rarely present as dominant strains. The last two types were frequently found in the dominant strains in tumor tissues. The overall prevalence of HBV carrying ΔSP was 17.64% (6/34) in tumor tissues, but none were dominant in non-tumor tissues. HBV carrying ΔSP was unable to produce S protein in vitro. Immunocytofluorescence assay showed that the ΔSP LHBs mutant aggregated in the cytoplasm, accumulating mainly in the ER. Transient transfection and expression of ΔSP mutant caused GRP78 up-regulation in vitro.