不同乳腺癌亚型中EB病毒感染相关分析及免疫微环境探索  

Correlation analysis of EBV infection in different subtypes of breast cancer and exploration of immune microenvironment

作　　者：杨春蓉[1] 陈路[1] 刘宇飞[1] 宋子华[1] 胡余昌[1] YANG Chunrong;CHEN Lu;LIU Yufei;SONG Zihua;HU Yuchang(Pathology Department of Yichang Central People’s Hospital,Yichang,Hubei 443001,China)

机构地区：[1]宜昌市中心人民医院病理科,湖北宜昌443001

出　　处：《中国优生与遗传杂志》2024年第2期255-260,共6页Chinese Journal of Birth Health & Heredity

基　　金：宜昌市卫生科技项目(A16-301-11)。

摘　　要：目的 分析不同乳腺癌亚型中EB(Epstein-Barr)病毒感染相关性,并探索EB病毒感染与免疫微环境关系。方法 共收集188例乳腺癌根治术后组织样本,采用免疫原位杂交(ISH)法检测乳腺标本组织中EB病毒编码的小RNA(EBER),利用TIMER 2.0数据库下载癌症基因组图谱(TCGA)中的乳腺癌样本的6类免疫细胞亚群分布,并进行不同乳腺癌亚型间免疫细胞分布差异比较;利用免疫组化进行HER-2阳性乳腺癌患者中LMP1和CD8表达观察,并利用Fisher’s确切概率进行相关性检验。结果 HER-2阳性乳腺癌患者ERBR阳性比率最高为42.9%,高于Luminal B型、Luminal A型和三阴性乳腺癌的22.6%、17.0%和14.3%(χ~2检验,P=0.011)。免疫微环境分析显示:三阴性乳腺癌患者中髓系树突状细胞(DC)、中性粒细胞和CD4阳性T细胞丰度均高于其他3型乳腺癌患者;HER-2阳性乳腺癌患者CD8阳性T细胞显著高于其他3型乳腺癌;Luminal A型和Luminal B型乳腺癌具有相对低的免疫细胞浸润丰度(Mann-Whitney U检验,P<0.05)。HER-2阳性乳腺癌患者进行LMP1和CD8免疫组化染色相关性检验显示:LMP1表达与CD8阳性T细胞浸润显著相关(χ~2=5.809;P=0.033)。结论 不同乳腺癌亚型中EB病毒感染存在差异,且对应不同的免疫微环境。HER-2阳性乳腺癌患者中EB病毒感染比率高,LMP1表达与CD8阳性细胞浸润相关,提示潜在免疫治疗获益可能。Objective To analyze the relationship between Epstein Barr virus infection in different subtypes of breast cancer and explore the relationship between Epstein Barr virus infection and immune microenvironment.Methods 188 tissue samples from breast cancer patients after radical surgery were collected,and the small RNA encoded by EBV(EBER) in the tissue samples was detected by in situ hybridization(ISH).The distribution of six types of immune cell subsets of breast cancer samples in the cancer genome map(TCGA) was downloaded from TIMER 2.0 database,and the differences in the distribution of immune cells among different breast cancer subtypes were compared;Immunohistochemistry was used to observe the expression of LMP1 and CD8 in HER-2 positive breast cancer patients,and Fisher's exact probability was used for correlation test.Results The positive rate of ERBR in HER-2 positive breast cancer patients was the highest(42.9%),higher than that in Luminal B,Luminal A and triple negative breast cancer patients(22.6%,17.0% and 14.3%)(χ~2 test,P=0.011).The immune microenvironment analysis showed that the abundance of myeloid dendritic cells(DC),neutrophils and CD4 positive T cells in triple negative breast cancer patients was higher than that in other type 3 breast cancer patients.The CD8 positive T cells in HER-2 positive breast cancer patients were significantly higher than those in other type 3 breast cancer patients.Luminal type A and Luminal type B breast cancer have relatively low infiltration abundance of immune cells(Mann-Whitney U test,P<0.05).The correlation test of LMP1 and CD8 immunohistochemical staining in HER-2 positive breast cancer patients showed that LMP1 expression was significantly correlated with CD8 positive T cell infiltration(χ~2=5.809;P=0.033).Conclusion EBV infection is different in different subtypes of breast cancer,and corresponds to different immune microenvironments.EB virus infection rate is high in HER-2 positive breast cancer patients,LMP1 expression is related to CD8 positive cell infilt

关 键 词：乳腺癌 EB病毒 免疫微环境 LMP1 

分 类 号：R737.9[医药卫生—肿瘤]