标题：基于生物信息学数据库研究NDC1基因在肝细胞肝癌组织中的表达水平及临床意义

      作者：许华，陈雨帆，周黛丽，李晓伟    许华，陈雨帆，周黛丽，李晓伟南京医科大学附属江苏盛泽医院普外科南京医科大学康达学院盛泽临床医学院，江苏 苏州 215228

      卷次： 2024年35卷2期

      【摘要】 目的 探讨肝细胞肝癌(LIHC)中NDC1基因的表达水平及临床价值。方法 利用 The HumanProtein Atlas、GEPIA、TIMER数据库在线分析NDC1基因在健康人体各器官组织、正常肝组织和肝细胞肝癌组织中的表达情况。利用Kaplan-Meier Ploter和UALCAN数据库的肝癌数据集在线分析患者NDC1表达与生存总周期的关系。通过STRING数据库在线检索NDC1的相关蛋白网络图，并进行功能注释和KEGG通路富集分析。通过TIMER数据库检测NDC1在肝癌中的免疫细胞的浸润水平以分析临床不良预后的相关性。结果 人体不同器官的NDC1 mRNA存在差异表达。与对照组相比，NDC1基因在乳腺癌、膀胱癌、结肠癌、胆管癌、肺鳞癌、肝癌的表达水平显著上升，且差异有显著统计学意义(P<0.001)。肝癌组织NDC1 mRNA的表达水平高于正常肝脏组织，肝癌组织中NDC1 mRNA表达水平明显上调，差异有统计学意义(P<0.05)。NDC1基因在正常肝组织中的表达水平为2.356(1.728~2.878)。根据病理分级，NDC1基因在1级肝癌组织中的表达水平为3.071 (2.475~4.981)，在2级肝癌组织中的表达水平为3.69 (2.457~5.305)，在3级肝癌组织中的表达水平为4.676 (2.745~6.874)，在4级肝癌组织中的表达水平为4.586 (3.159~6.954)，各级肝癌中NDC1的表达水平差异有显著统计学意义(P<0.01)；根据肿瘤临床分期，NDC1基因在Ⅰ期肝癌组织中表达水平为3.323 (2.371~5.414)，在Ⅱ期肝癌组织中表达水平为4.294 (2.704~7.496)，在Ⅲ期肝癌组织中表达水平为4.684 (2.979~7.037)，在Ⅳ期肝癌组织中表达水平为1.983 (1.801~2.669)，肝癌Ⅰ、Ⅱ和Ⅲ期中NDC1基因的表达水平均显著高于正常组织(P<0.001)，而肝癌Ⅱ期和Ⅲ期中的表达水平显著高于Ⅰ期，差异具有显著统计学意义(P<0.01)；根据身体质量指数分组，在正常体质量的肝癌组织表达水平为3.62 (2.584~5.661)，在超常体质量的肝癌组织表达水平为3.841 (2.098~6.056)，在肥胖的肝癌组织表达水平为3.627 (2.504~5.182)，在极度肥胖的肝癌组织表达水平为3.577 (2.359~4.909)。任何BMI患者的肝癌组织中NDC1的表达水平均显著高于正常肝脏组织，差异具有显著统计学意义(P<0.01)。NDC1与CDK1、CCNB1、CCNB2、SEH1L、NUP155、CDCA8等蛋白相关，NDC1 mRNA在肝癌免疫微环境中与CD8+ T细胞、CD4+ T细胞、T细胞、B细胞、中性粒细胞、单核细胞、巨噬细胞和骨髓细胞等免疫细胞中的表达呈正相关性(P<0.05)。结论 肝癌组织中NDC1基因呈现高表达水平，其表达水平与肝癌的发生、发展及预后密切相关，可能是肝癌潜在的预后生物学标志物及治疗靶标。
      【关键词】 肝细胞肝癌；NDC1基因；预后；生物信息学
      【中图分类号】 R735.7 【文献标识码】 A 【文章编号】 1003—6350（2024）02—0153—07

Expression level and clinical significance of NDC1 gene in hepatocellular carcinoma based on bioinformaticsdatabase.
XU Hua, CHEN Yu-fan, ZHOU Dai-li, LI Xiao-wei. Department of General Surgery, the Affiliated JiangsuShengze Hospital of Nanjing Medical University, Suzhou 215228, Jiangsu, CHINA
【Abstract】 Objective To investigate the expression level and clinical value of NDC1 gene in hepatocellularcarcinoma (LIHC). Methods The expression of NDC1 gene in healthy human organ tissues, normal liver tissues, andhepatocellular hepatocellular carcinoma tissues was analyzed online using The Human Protein Atlas, GEPIA, and TIM-ER databases. The relationship between NDC1 expression and overall survival cycle in patients was analyzed online us-ing the hepatocellular carcinoma dataset from the Kaplan-Meier Ploter and UALCAN databases. The network map of re-lated proteins of NDC1 was retrieved online by STRING database and analyzed by functional annotation and KEGGpathway enrichment. The infiltration level of NDC1 in immune cells in hepatocellular carcinoma was detected by TIM-ER database to analyze the correlation of poor clinical prognosis. Results There is differential expression of NDC1mRNA in different organs of the human body. Compared with the control group, the expression level of NDC1 gene inbreast cancer, bladder cancer, colon cancer, cholangiocarcinoma, lung squamous cell carcinoma, and liver cancer in-creased significantly, and the difference was statistically significant (P<0.001). The expression level of NDC1 mRNA inliver cancer tissue is higher than that in normal liver tissue, and the expression level of NDC1 mRNA in liver cancer tis-sue is significantly upregulated, with statistically significant differences (P<0.05). The expression level of NDC1 gene innormal liver tissue was 2.356 (1.728-2.878). According to pathological grading, the expression level of NDC1 gene was3.071 (2.475-4.981) in grade 1 liver cancer tissue, 3.69 (2.457-5.305) in grade 2 liver cancer tissue, 4.676 (2.745-6.874)in grade 3 liver cancer tissue, and 4.586 (3.159-6.954) in grade 4 liver cancer tissue. The expression level difference ofNDC1 in all grades of liver cancer tissue was statistically significant (P<0.01). According to the clinical staging of tu-mors, the expression level of NDC1 gene was 3.323 (2.371-5.414) in stage Ⅰ liver cancer tissue, 4.294 (2.704-7.496)in stage Ⅱ liver cancer tissue, 4.684 (2.979-7.037) in stage Ⅲ liver cancer tissue, and 1.983 (1.801-2.669) in stage Ⅳliver cancer tissue. The expression level of NDC1 gene in stages Ⅰ, Ⅱ, and Ⅲ liver cancer tissue was significantlyhigher than that in normal tissue (P<0.001). The expression levels in stage Ⅱ and Ⅲ of liver cancer were significantlyhigher than those in stage Ⅰ, and the difference was statistically significant (P<0.01). According to the body mass in-dex grouping, the expression level of NDC1 gene was 3.62 (2.584-5.661) in normal weight liver cancer tissue, 3.841(2.098-6.056) in overweight liver cancer tissue, 3.627 (2.504-5.182) in obese liver cancer tissue, and 3.577(2.359-4.909) in extremely obese liver cancer tissue. The expression level of NDC1 in liver cancer tissue of patientswith abnormal BMI was significantly higher than that in normal liver tissue (P<0.01). NDC1 is associated with proteinssuch as CDK1, CCNB1, CCNB2, SEH1L, NUP155, CDCA8, etc. NDC1 mRNA is positively correlated with the ex-pression of CD8+ T cells, CD4+ T cells, T cells, B cells, neutrophils, monocytes, macrophages, and bone marrow cellsin the immune microenvironment of liver cancer (P<0.05). Conclusion NDC1 gene showed high expression level inhepatocellular carcinoma tissues, and its expression level was closely related to the occurrence, development, and prog-nosis of hepatocellular carcinoma, which may be a potential prognostic biological marker and therapeutic target of he-patocellular carcinoma.
      【Key words】 Hepatocellular carcinoma; NDC1 gene; Prognosis; Bioinformatics