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

作　　者：王述莲 徐朝 郑继伟 王晓枫 顾文刚 李绵洋[2] 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.)

机构地区：[1]武警北京市总队医院检验与病理科,北京100027 [2]解放军总医院医学检验中心

出　　处：《中西医结合肝病杂志》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)。

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(p

关 键 词：肝癌 Kruppel样因子6 核小体组装蛋白1-like-1 

分 类 号：R735.7[医药卫生—肿瘤]