引用本文:罗 鑫,沈 宁,刘 畅,张 沅,林丽娜,李 枫,李冰滢,肖绍文,陈 芳,张庆梅.肿瘤相关抗原MAGE-D4在肝细胞癌中的表达及其意义[J].中国临床新医学,2021,14(6):594-599.
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肿瘤相关抗原MAGE-D4在肝细胞癌中的表达及其意义
罗 鑫,沈 宁,刘 畅,张 沅,林丽娜,李 枫,李冰滢,肖绍文,陈 芳,张庆梅
530021 南宁,广西医科大学组织学与胚胎学教研室(罗 鑫,张 沅,林丽娜,李 枫,李冰滢,陈 芳,张庆梅);530021 南宁,广西壮族自治区人民医院口腔颌面外科(沈 宁);530021 南宁,广西医科大学第一附属医院神经外科(刘 畅,肖绍文)
摘要:
[摘要] 目的 探讨肿瘤相关抗原MAGE-D4在肝细胞癌(HCC)中的表达情况,并分析其临床意义。方法 基于癌症基因组图谱(TCGA)数据库,获取371例HCC组织和50例正常肝组织的转录数据。应用数据挖掘工具UALCAN分析HCC组织中MAGE-D4 mRNA的表达情况,并筛选与其表达相关的基因。应用Kaplan-Meier Plotter分析MAGE-D4 mRNA表达水平与患者生存预后的关系。另收集于广西医科大学第一附属医院2009年6月至2011年8月经手术获取的HCC标本70例,癌旁组织标本30例,采用免疫组织化学法(IHC)检测MAGE-D4蛋白的表达情况,并分析其与患者临床指标的关联性。结果 基于TCGA数据库数据的分析结果显示,MAGE-D4 mRNA在HCC组织中的表达水平显著高于正常肝组织(P<0.05),且与甲胎蛋白(AFP)mRNA表达呈正相关(r=0.556,P=0.000)。生存分析结果显示,MAGE-D4 mRNA高表达与黄种人HCC患者不良生存预后具有显著关联(HR=1.860,P=0.037)。基于临床获取标本的分析结果显示,MAGE-D4蛋白主要定位于细胞质和细胞核,HCC组织的MAGE-D4高表达率显著大于癌旁组织(48.57% vs 23.33%; χ2=5.530,P=0.019)。MAGE-D4高表达组HCC患者血清AFP浓度≥400 μg/L的人数比例显著大于低表达组(P<0.05),但两组在性别、年龄、肿瘤级别、肿瘤分期、肿瘤直径、癌栓和乙型肝炎病毒(HBV)感染等方面比较差异无统计学意义(P>0.05)。结论 MAGE-D4在HCC组织中高表达,其可能在HCC的发生和发展过程中发挥重要作用,有望成为HCC的潜在治疗靶点和预后标志物。
关键词:  肝细胞癌  MAGE-D4  癌症基因组图谱数据库  临床特征  预后
DOI:10.3969/j.issn.1674-3806.2021.06.15
分类号:R 735.7
基金项目:国家自然科学基金资助项目(编号:81560408);广西自然科学基金资助项目(编号:2018GXNSFAA050058);广西区域性高发肿瘤早期防治研究教育部重点实验室和广西重点实验室自主研究课题(编号:GEK2019-08)
Expression of tumor-associated antigen MAGE-D4 in hepatocellular carcinoma and its significance
LUO Xin, SHEN Ning, LIU Chang, et al.
Department of Histology and Embryology, Guangxi Medical University, Nanning 530021, China
Abstract:
[Abstract] Objective To explore the expression of tumor-associated antigen melanoma-associated antigen family member D4(MAGE-D4) in hepatocellular carcinoma(HCC) and to analyze its clinical significance. Methods Based on the cancer genome atlas(TCGA) database, the transcription data of 371 cases of HCC tissues and 50 cases of normal liver tissues were obtained. The data mining tool UALCAN was used to analyze the expression of MAGE-D4 mRNA in HCC tissues, and to screen the genes related to the MAGE-D4 mRNA expression. Kaplan-Meier Plotter was used to analyze the relationship between MAGE-D4 mRNA expression level and the patients′ survival prognosis. In addition, 70 HCC specimens and 30 paracancerous tissue specimens were collected from the First Affiliated Hospital of Guangxi Medical University during June 2009 and August 2011. The expression of MAGE-D4 protein was detected by immunohistochemistry(IHC), and the correlation between the expression of MAGE-D4 protein and the patients′ clinical indicators was analyzed. Results The data analysis based on the TCGA database showed that the expression level of MAGE-D4 mRNA in the HCC tissues was significantly higher than that in the normal liver tissues(P<0.05), and was positively correlated with alpha fetoprotein(AFP) mRNA expression(r=0.556, P=0.000). The results of survival analysis showed that the high expression of MAGE-D4 mRNA was significantly associated with the poor survival prognosis of yellow race HCC patients(HR=1.860, P=0.037). The analysis results based on the clinical specimens showed that MAGE-D4 protein was mainly located in the cytoplasm and nucleus, and the high expression rate of MAGE-D4 in the HCC tissues was significantly higher than that in the adjacent tissues(48.57% vs 23.33%; χ2=5.530, P=0.019). The proportion of HCC patients with serum AFP concentration ≥400 μg/L in MAGE-D4 high expression group was significantly greater than that in low expression group(P<0.05), but there was no statistically significant difference between the two group in gender, age, tumor grade, tumor stage, tumor diameter, tumor thrombus and hepatitis B virus(HBV) infection(P>0.05). Conclusion MAGE-D4 is highly expressed in HCC tissues, which may play an important role in the occurrence and development of HCC, and is expected to become a potential therapeutic target and a prognostic marker for HCC.
Key words:  Hepatocellular carcinoma(HCC)  Melanoma-associated antigen family member D4(MAGE-D4)  
The Cancer Genome Atlas(TCGA) database
  Clinical feature  Prognosis