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KLF6、NAP1L1表达与肝癌患者病理特征的相关性及对预后的影响

The correlation between the expression of KLF6 and NAP1L1 and the pathological characteristics of liver cancer patients and their impact on prognosis
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摘要 目的:探讨Kruppel样因子6(KLF6)蛋白与核小体组装蛋白1-like-1(NAP1L1)在肝癌中的表达规律及其与肝癌病理特征及临床预后之间的关系。方法:采用免疫组化法检测202例肝癌和癌旁组织以及78例正常肝组织中KLF6、NAP1L1的表达情况。结果:202例肝癌组织中,KLF6和NAP1L1阳性表达率分别为41.09%(83例)和96.53%(195例)。癌旁组织和正常肝组织中,KLF6阳性表达率分别为81.19%(164例)和100%(78例),NAP1L1完全不表达。KLF6表达在AFP<400μg/L、无HBV感染、肿瘤直径<5 cm、高分化程度及TMN分期Ⅰ期患者中阳性率偏高(P<0.05)。NAP1L1在AFP≥400μg/L、肝硬化、肿瘤直径>5 cm、HBV感染及TNM分期Ⅲ期患者中阳性率偏高(P>0.05)。KLF6表达与AFP、肿瘤直径、肝硬化、HBV感染、分化程度、TNM分期呈显著负相关(P<0.05);NAP1L1表达与AFP、肿瘤直径、肝硬化、HBV感染、TNM分期呈显著正相关(P<0.05)。KLF6阴性和NAP1L1阳性患者中复发占比偏高(P<0.05)。AFP≥400μg/L、肿瘤直径≥5 cm、肝硬化、HBV感染、分化程度(低分化)、TNM分期(Ⅲ~Ⅲ期)、NAP1L1表达(阳性)是肿瘤复发的危险因素(P<0.05),KLF6表达(阳性)是肿瘤复发保护因素(P<0.05)。202例肝癌患者进行随访生存分析,半年生存率为87.62%,1年生存率为69.31%,1.5年生存率为59.41%。KLF6阳性患者生存时间长于阴性患者,NAP1L1阴性患者生存时间长于阳性患者。ROC曲线结果显示,NAP1L1诊断肝癌曲线下面积(AUC)为0.754,最佳界值为0.619,敏感度为63.8%,特异性为85.1%,Cut-off为8.052;KLF6诊断肝癌AUC为0.835,敏感度为64.2%,特异性为93.1%。两者联合诊断肝癌的AUC为0.890,最佳界值为0.721,敏感度为59.3%,特异性为98.6%,Cut-off为7.418。结论:转录因子KLF6、NAP1L1可能在肝癌病情发展中发挥重要作用,两者异常表达多合并低AFP水平、HBV感染、低分化程度等特征,且与患者不良预后相关。 Objective:To investigate the expression of Kruppel like factor 6(KLF6)protein and nucleosome assembly protein 1-like-1(nap1l)in hepatocellular carcinoma(HCC)and their relationship with clinical prognosis of HCC.Methods:Immunohistochemistry was used to detect KLF6 and NAP1L1 expression in 202 hepatocellular carcinoma and paracancer tissues and 78 donor livers.Results:The positive expression rate of KLF6 was 41.09%(83 cases),and the positive expression rate of NAP1L1 was 96.53%(195 cases).In 202 cases,the positive expression rate of KLF6 was 81.19%(164 cases),and NAP1L1 was not expressed at all.In normal liver tissues,KLF6 positive expression rate was 100%(78 cases),NAP1L1 was not expressed at all.The positive rate of KLF6 expression was higher in AFP<400μg/L group.The positive rate of KLF6 in HBV infection group was higher than that in non-HBV infection group(P<0.05).The positive rate of KLF6 was higher in the highly differentiated group(P<0.05).In the TMN stage group,the positive rate of KLF6 in stageⅠwas high(P<0.05).The positive rate of NAP1L1 was higher in AFP≥400μg/L group.The positive rate of NAP1L1 was higher in cirrhosis group.The positive rate was higher in the direct larger tumor group(P<0.05).The positive rate of HBV infection was higher(P<0.05).The positive rate in TNM stage III was higher(P<0.05).Spearman correlation analysis showed that KLF6 was significantly negatively correlated with AFP,tumor diameter,HBV infection,differentiation degree and TNM stage(P<0.05).NAP1L1 was positively correlated with AFP,tumor diameter,liver cirrhosis,HBV infection and TNM stage(P<0.05).The proportion of recurrence in KLF6 negative patients was higher(P<0.05).NAP1L1 positive patients accounted for a high proportion of positive.Cox multivariate analysis of tumor recurrence showed that AFP≥400(μg/L),tumor diameter≥5 cm,liver cirrhosis,HBV infection,differentiation degree(low differentiation),TNM stage(Ⅲ-Ⅲstage),NAP1L1 expression(positive)were the risk factors for tumor recurrence(P<0.05).KLF6 expression(positive)was a protective factor for tumor recurrence(P<0.05).The survival rate of 202 patients with liver cancer was 87.62%in six months,69.31%in one year and 59.41%in 1.5 years.Survival analysis showed that patients with negative KLF6 and NAP1L1 had a longer survival time than those with positive KLF6 and NAP1L1.The median survival time of KLF6-positive patients with liver cancer was 41.05 months and that of negative patients was 54.15 months.The median survival time of patients with NAP1L1 positive liver cancer was 44.97 months,and that of patients with NAP1L1 negative liver cancer was 57.20 months,the difference was statistically significant.ROC curve results showed that the area under the curve(AUC)of NAP1L1 was 0.754,the optimal Cut-off value was 0.619,the sensitivity was 63.8%,the specificity was 85.1%,and the cut-off was 8.052.The AUC of KLF6 was 0.835,the sensitivity was 64.2%,and the specificity was 93.1%.The AUC of the combined diagnosis of liver cancer was 0.890,the optimal Cut-off value was 0.721,the sensitivity was 59.3%,the specificity was 98.6%,and the cut-off was 7.418.Conclusion:Transcription factors KLF6 and NAP1L1 may play important roles in the development of liver cancer,and their abnormal expression is often associated with low AFP levels,HBV infection,low differentiation,and is associated with poor prognosis in patients.
作者 王述莲 徐朝 郑继伟 王晓枫 顾文刚 李绵洋 WANG Shu-lian;XU Zhao;ZHENG Ji-wei;GU Wen-gang(Laboratory Medicine and Pathology Department of Beijing Armed Police Corps Hospital(Beijing,100853),China.)
出处 《中西医结合肝病杂志》 CAS 2024年第12期1120-1126,共7页 Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
基金 解放军总医院临床科研扶持基金(No.2016FC-TSYS-2040)。
关键词 肝癌 Kruppel样因子6 核小体组装蛋白1-like-1 liver cancer Kruppel like factor 6 protein and nucleosome assembly protein 1-like-1
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