肝细胞癌中NCAPD2的表达及临床意义

Expression and clinical significance of NCAPD2 in hepatocellular carcinoma

目的探讨染色体凝缩蛋白复合物Ⅰ的亚基D2(non-SMC condensinⅠcomplex subunit D2,NCAPD2)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的临床价值。方法应用UALCAN数据库分析正常肝组织和HCC组织中NCAPD2 mRNA的表达及其与临床病理学特征的关系;应用免疫组化SP两步法检测正常肝组织和HCC组织中NCAPD2蛋白的表达,并分析其与临床病理学特征之间的相关性;应用GEPIA和Oncolnc数据库分析NCAPD2 mRNA表达与HCC患者生存期的关系;运用GO富集分析和STRING数据库筛查NCAPD2可能参与的生物学功能及蛋白互作关系。结果UALCAN数据库分析结果显示,NCAPD2 mRNA表达在HCC组织中显著增强,其高表达与HCC临床分期、组织学分级和TP53突变呈正相关(P<0.05)。免疫组化结果显示,NCAPD2在低分化癌中的强阳性率(68.0%,17/25)明显高于中分化(34.0%,14/41)和高分化癌(25.0%,1/4)(P<0.05),NCAPD2蛋白在临床分期Ⅲ+Ⅳ期HCC组织中的强阳性率(55.0%,33/60)明显高于Ⅰ+Ⅱ期HCC组织(20.0%,2/10)(P<0.05)。与癌旁组织相比,HCC组织中NCAPD2蛋白表达水平显著升高(P<0.01),且与HCC组织学分级和临床分期关系密切。生存分析结果显示,NCAPD2高表达组患者的总生存率和无瘤生存率均显著低于低表达组(P<0.05)。生信分析结果显示,NCAPD2主要参与肿瘤的细胞周期和增殖等生物学功能,并与细胞周期进程相关蛋白相互作用。结论NCAPD2在HCC中异常表达且发挥重要作用,可能作为HCC早期诊断生物标志物及药物治疗新靶点。

Purpose To observe the clinical value of non-SMC condensin Ⅰ complex subunit D2(NCAPD2)in hepatocellular carcinoma(HCC).Methods The expression of NCAPD2 mRNA in normal and HCC tissues and its relationship with clinicopathological features was analyzed by UALCAN database.Immunohistochemical SP two-step staining was used to detect the expression of NCAPD2 protein in normal and HCC tissues,and to analyze the correlation between the NCAPD2 expression and clinicopathological features.GEPIA and Oncolnc database were used to analyze relationship between the expression of NCAPD2 mRNA and the survival of HCC patients.The possible biological functions and protein interactions of NCAPD2 were revealed by GO enrichment analysis and STRING database.Results The analysis of UALCAN database showed that the expression of NCAPD2 mRNA was significantly increased in HCC,and its overexpression was closely related to clinical stage,histological grade and TP53 mutation(P<0.05).The results of immunohistochemistry showed that the strong positive rate of NCAPD2 protein in poorly differentiated HCCs(68.0%,17/25)was significantly higher than that in moderately differentiated(34.0%,14/41)and highly differentiated HCCs(25.0%,1/4)(P<0.05).The strong positive rate of NCAPD2 protein in clinical stage Ⅲ+Ⅳ HCC tissues(55.0%,33/60)was significantly higher than that in stage Ⅰ+Ⅱ HCC tissues(20.0%,2/10)(P<0.05).The expression level of NCAPD2 protein in HCC tissues was significantly higher than in adjacent tissues(P<0.01).Survival analysis showed that the survival rate of patients with high expression of NCAPD2 was significantly lower than patients with low expression of NCAPD2(P<0.05).Bioinformatics analysis showed NCAPD2 was mainly involved in the biological functions of tumor cell cycle and proliferation,and interacted with cell cycle progression related proteins.Conclusion NCAPD2 is abnormally expressed in HCC and plays an important role.It may be used as a biomarker for early diagnosis of HCC and a new target for drug therapy.