OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups:...OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.展开更多
目的探讨中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)联合血小板/淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)评分对肝细胞癌肝移植受者预后的影响。方法回顾性分析2015年7月至2021年10月于河北医科大学第三医...目的探讨中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)联合血小板/淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)评分对肝细胞癌肝移植受者预后的影响。方法回顾性分析2015年7月至2021年10月于河北医科大学第三医院因肝细胞癌行肝移植的110例受者的临床资料,计算术前最近一次的NLR、PLR,通过受试者工作特征曲线(ROC曲线)得到NLR、PLR截断值,并根据截断值进行分组,将NLR<3.37、PLR<105.96记为0分,NLR≥3.37、PLR≥105.96记为1分,两者相加为NLR-PLR评分,依据NLR-PLR评分将受者分为3组,即0分组、1分组、2分组,用Kaplan-Meier法分析受者生存时间,组间对比执行Log-rank检验,基于Cox比例风险回归模型进行单因素及多因素分析。结果NLR-PLR评分为0分者中位总生存时间(overall survival,OS)为27个月,1分者为26.5个月,2分者为6个月,NLR-PLR 2分者中位OS明显短于0分及1分者,差异有统计学意义(P<0.001),NLR-PLR 0分组中位无病生存时间(disease-free survival,DFS)为24.5个月,NLR-PLR 1分组中位DFS为24个月,NLR-PLR 2分组中位DFS为6个月,差异有统计学意义(P=0.002)。单因素分析显示Child-Pugh分级、终末期肝病模型(MELD)评分、NLR水平、PLR水平、NLR-PLR评分、是否符合美国加州大学旧金山分校标准(University of california san francisco criteria,UCSF)、是否有微血管侵犯(microvascular invason,MVI)对肝细胞癌肝移植受者的远期存活率有影响,进一步多因素分析显示NLR-PLR评分、是否符合UCSF标准、MELD评分是影响受者预后生存的独立危险因素。结论NLR、PLR、NLR-PLR评分可以预测受者远期生存状况,其中NLR-PLR评分是影响受者生存的独立危险因素,且较NLR、PLR更有预测价值。展开更多
基金This study was supported by a grant from the National Natural Science Foundation of China(No. 39260033)and a grant from Guangxi Science Foundation, China (No. 0143058).
文摘OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.
文摘目的探讨中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)联合血小板/淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)评分对肝细胞癌肝移植受者预后的影响。方法回顾性分析2015年7月至2021年10月于河北医科大学第三医院因肝细胞癌行肝移植的110例受者的临床资料,计算术前最近一次的NLR、PLR,通过受试者工作特征曲线(ROC曲线)得到NLR、PLR截断值,并根据截断值进行分组,将NLR<3.37、PLR<105.96记为0分,NLR≥3.37、PLR≥105.96记为1分,两者相加为NLR-PLR评分,依据NLR-PLR评分将受者分为3组,即0分组、1分组、2分组,用Kaplan-Meier法分析受者生存时间,组间对比执行Log-rank检验,基于Cox比例风险回归模型进行单因素及多因素分析。结果NLR-PLR评分为0分者中位总生存时间(overall survival,OS)为27个月,1分者为26.5个月,2分者为6个月,NLR-PLR 2分者中位OS明显短于0分及1分者,差异有统计学意义(P<0.001),NLR-PLR 0分组中位无病生存时间(disease-free survival,DFS)为24.5个月,NLR-PLR 1分组中位DFS为24个月,NLR-PLR 2分组中位DFS为6个月,差异有统计学意义(P=0.002)。单因素分析显示Child-Pugh分级、终末期肝病模型(MELD)评分、NLR水平、PLR水平、NLR-PLR评分、是否符合美国加州大学旧金山分校标准(University of california san francisco criteria,UCSF)、是否有微血管侵犯(microvascular invason,MVI)对肝细胞癌肝移植受者的远期存活率有影响,进一步多因素分析显示NLR-PLR评分、是否符合UCSF标准、MELD评分是影响受者预后生存的独立危险因素。结论NLR、PLR、NLR-PLR评分可以预测受者远期生存状况,其中NLR-PLR评分是影响受者生存的独立危险因素,且较NLR、PLR更有预测价值。
