Title单中心大样本Epstein-Barr病毒相关性胃癌亚型的临床病理及分子特征分析
Other TitlesClinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation
Authors杨阳
刘毅强
王晓红
季科
李忠武
白健
杨爱蓉
胡颖
韩海勃
李子禹
步召德
吴晓江
张连海
季加孚
Affiliation北京大学肿瘤医院暨北京市肿瘤防治研究所恶性肿瘤发病机制及转化研究教育部重点实验室胃肠肿瘤中心
北京大学肿瘤医院暨北京市肿瘤防治研究所恶性肿瘤发病机制及转化研究教育部重点实验室病理科
北京大学肿瘤医院暨北京市肿瘤防治研究所恶性肿瘤发病机制及转化研究教育部重点实验室生物样本库
和瑞基因科技有限公司
KeywordsEpstein-Barr病毒感染
胃肿瘤
临床病理特征
预后
Epstein-Barr virus infections
Stomach neoplasms
Clinicopathological features
Prognosis
Issue Date2019
Publisher北京大学学报(医学版)
Abstract目的:Epstein-Barr病毒相关性胃癌(Epstein-Barr virus associated gastric cancer,EBVa GC)与常见胃癌(非Epstein-Barr病毒相关性胃癌,Epstein-Barr virus non-associated gastric cancer,EBVn GC)不同,具有独特的临床病理特征,本研究采用单中心大样本探讨中国EBVa GC的临床病理及分子特征。方法:回顾分析2003—2018年北京大学肿瘤医院EBVa GC与EBVn GC两组患者的临床病理特征和预后。分析公共数据库胃癌数据集,筛选显著差异表达基因,并在本组病例中验证重要基因的表达及其与预后的相关性。结果:3 241例胃癌患者纳入研究,EBVa GC为163例,占总数的5. 0%。与EBVn GC相比,EBVa GC男性常见,平均年龄低,多见于残胃癌,常为低分化腺癌、Lauren混合型,较少出现淋巴结转移,EBVa GC患者的5年生存率为63. 2%,优于EBVn GC的59. 6%(P <0. 05)。为挖掘EBVa GC的分子特征,对癌症基因组图谱(The Cancer Genome Atlas,TCGA)胃癌数据集(n=240)进行分析,筛选到7 404个显著差异表达基因,涉及细胞增殖、凋亡、侵袭转移等功能,其中侵袭转移相关基因SALL4下调、免疫检查点相关基因PD-L1上调是EBVa GC重要的分子特征。大样本验证显示,SALL4在EBVa GC中多为阴性(1/92,1. 1%,低于EBVn GC的303/1 727,17. 5%),PD-L1在EBVa GC中多为阳性(81/110,73. 6%,高于EBVn GC的649/2 350,27. 6%),SALL4阴性和PD-L1阳性患者的预后较好。结论:EBVa GC作为独特的胃癌亚型,较少出现转移且预后良好,该亚型具有特征性分子背景,其中侵袭转移相关基因SALL4的下调以及免疫检查点相关基因PD-L1的上调是重要的分子特征。
Objective: Epstein-Barr virus associated gastric cancer( EBVaGC) is different from the traditional gastric cancer( Epstein-Barr virus non-associated gastric cancer,EBVnGC),and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. Methods: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer( GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital.Results: In this study,3 241 GC patients were included,and a total of 163 EBVaGC( 5. 0%) patients were identified. Compared with EBVnGC,EBVaGC was higher in male and younger patients,and positively associated with remnant GC,poorly differentiated adenocarcinoma,and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was59. 6% and 63. 2% respectively( P < 0. 05). In order to explore molecular features of EBVaGC,the Cancer Genome Atlas( TCGA) dataset was analyzed( n = 240),and 7 404 significant differentially expressed genes were obtained,involving cell proliferation,apoptosis,invasion and metastasis. The downregulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative( 1/92,1.1%, lower than EBVnGC,303/1 727,17. 5%),and that PD-L1 was mostly positive in EBVaGC( 81/110,73. 6%,higher than EBVnGC,649/2 350,27. 6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. Conclusion: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
URIhttp://hdl.handle.net/20.500.11897/563766
ISSN1671-167X
DOI10.19723/j.issn.1671-167X.2019.03.012
Indexed中文核心期刊要目总览(PKU)
Appears in Collections:北京肿瘤医院

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