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[1]郭晶晶,徐瀚峰,朱传东,等.N-myc下游调控基因1在肝细胞癌中的表达及其与预后的相关性[J].医学研究与战创伤救治(原医学研究生学报),2021,23(01):21-27.[doi:10.3969/j.issn.1672-271X.2021.01.001]
　GUO Jing-jing,XU Han-feng,ZHU Chuan-dong,et al.The expression and prognosis of NDRG1 in hepatocellular carcinoma[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2021,23(01):21-27.[doi:10.3969/j.issn.1672-271X.2021.01.001]
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N-myc下游调控基因1在肝细胞癌中的表达及其与预后的相关性()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第23卷
期数:
2021年01期
页码:
21-27
栏目:
临床研究
出版日期:
2021-01-20

文章信息/Info

Title:
The expression and prognosis of NDRG1 in hepatocellular carcinoma
作者:
郭晶晶; 徐瀚峰; 朱传东; 缪祎; 郑勤
作者单位：210003南京，南京中医药大学附属南京医院（南京市第二医院）肿瘤科（郭晶晶、徐瀚峰、朱传东、郑勤）;210029南京，南京医科大学第一附属医院（江苏省人民医院）血液科（缪祎）
Author(s):
GUO Jing-jing1; XU Han-feng1; ZHU Chuan-dong1; MIAO Yi2; ZHENG Qin1
(1. Department of Oncology，Nanjing Second Hospital，Nanjing University of Chinese Medicine， Nanjing 210003，Jiangsu，China; 2. Department of Hematology，the First Affiliated Hospital of Nanjing Medical University/Jiangsu Province People Hospital，Nanjing 210029，Jiangsu，China)
关键词:
N-myc下游调控基因1; 肝细胞癌; 基因表达; 预后
Keywords:
NDRG1;  hepatocellular carcinoma;  gene expression;  prognosis
分类号:
R735.7
DOI:
10.3969/j.issn.1672-271X.2021.01.001
文献标志码:
A
摘要:
目的肝细胞癌(HCC)是肝最常见的原发性恶性肿瘤之一。N-myc下游调控基因1(NDRG1)在肝癌中的作用尚存争议。文章旨在证实NDRG1在HCC患者中的表达及其预后价值、潜在的生物学功能以及对免疫系统的影响。方法选择TCGA数据库中的肝癌数据，包括58例正常肝组织标本和407例肝癌标本及与之相应的临床资料，对NDRG1基因在正常肝组织和肝癌组织中的表达进行分析。使用GTEx数据库显示NDRG1在人类肝组织中的表达。利用HPA分析NDRG1蛋白在HCC的表达情况。根据NDRG1表达的中位数，将所有患者分为NDRG1低表达组和NDRG1高表达组，并分析2组的生存情况。分析NDRG1表达与组织学分级（G）、临床S分期、临床T分期相关性。通过GSEA富集分析KEGG通路，探讨NDRG1的生物学功能。使用TIMER和CIBERSORT来分析HCC中NDRG1与免疫浸润细胞的相关性。结果与正常肝组织相比，肝癌组织中NDRG1表达增加(P<0.001)。NDRG1表达与组织学分级（G）(P<0.001)、临床S分期(P=0.03)、临床T分期(P=0.018)呈正相关。NDRG1的高表达与较差的总生存率显著相关(P=0.005)。单因素Cox分析分析显示NDRG1高表达与较差的总生存率显著相关(P<0.001)。多因素Cox分析分析表明,高NDRG1表达是独立危险因素，与肝细胞癌患者的总生存期密切相关(P<0.001)。通过GSEA分析，发现NDRG1可能通过DNA修复、E2F、MYC-V1、G2M检查点、P53通路、TGF-β通路等途径调控肿瘤的发生发展。TIMER和CIBERSORT分析显示NDRG1的高表达与M0巨噬细胞呈正相关。结论NDRG1在肝癌组织中高表达，提示预后不佳。可能通过肿瘤免疫浸润细胞改变肿瘤微环境促进肝癌的发生发展。NDRG1可作为HCC预后的生物学标志物。
Abstract:
ObjectiveHepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver. The role of N-myc downstream regulatory gene 1 (NDRG1) in HCC is still controversial. The purpose of this study was to confirm the expression of NDRG1 in HCC patients and its prognostic value，potential biological functions, and effects on the immune system.MethodsThe expression of NDRG1 gene in normal liver tissues and liver cancer tissues was analyzed using the data of liver cancer from TCGA database (58 normal liver samples and 407 liver cancer samples). The expression of NDRG1 in human liver tissues was shown using the GTEx database. HPA was used to analyze the expression of NDRG1 protein in HCC. According to the median NDRG1 expression，all patients were divided into NDRG1 low-expression group and NDRG1 high-expression group. The survival of NDRG1 low expression group and NDRG1 high expression group were analyzed. The correlation between NDRG1 expression and histological grade，S stage and T stage was analyzed. The biological function of NDRG1 was studied by GSEA enrichment analysis of KEGG pathway. TIMER and CIBERSORT were used to analyze the correlation between NDRG1 and immune-infiltrating cells in HCC.ResultsNDRG1 expression was increased in liver cancer compared with normal liver tissue (P<0.001). NDRG1 expression was positively correlated with histological grade (G) (P<0.001)，clinical S stage (P=0.03)，and clinical T stage (P=0.018). High NDRG1 expression was significantly associated with poor overall survival (P=0.005). Univariate Cox analysis showed that high NDRG1 expression was significantly associated with poor overall survival (P<0.001). Multivariate Cox analysis showed that high NDRG1 expression was an independent risk factor and was closely associated with overall survival in HCC patients (P<0.001). Through GSEA analysis，we found that NDRG1 regulated the occurrence and development of tumors through DNA repair，E2F，MYC-V1，G2M checkpoint，P53 pathway，TGF-pathway and other pathways. TIMER and CIBERSORT analysis showed that NDRG1 expression was positively correlated with M0 macrophages.ConclusionNDRG1 is highly expressed in liver cancer tissues，suggesting a poor prognosis. NDRG1 may promote the development of hepatocellular carcinoma by changing tumor microenvironment through tumor immune infiltrating cells. NDRG1 can be used as a biomarker for prognosis of HCC.

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备注/Memo

备注/Memo:
基金项目：“十三五”南京市医学科技发展资金重大项目（ZDX16008）；南京市医学科技发展重点项目（ZKX19043）
更新日期/Last Update: 2021-01-26