GAS1与乳腺癌免疫治疗及药物敏感性的关系  

Relationship between GAS1,immunotherapy and drug sensitivity in breast cancer

作　　者：鲁泓男 夏冰舒 乔坤 张世园 黄元夕[1] 鲁祥石[1] LU Hongnan;XIA Bingshu;QIAO Kun;ZHANG Shiyuan;HUANG Yuanxi;LU Xiangshi(Department of Breast Surgery,Harbin Medical University Cancer Hospital,Harbin,150081,China)

机构地区：[1]哈尔滨医科大学附属肿瘤医院乳腺外科,哈尔滨150081

出　　处：《实用肿瘤学杂志》2023年第4期351-359,共9页Practical Oncology Journal

基　　金：北京迈迪科公益基金会科研项目(编号:MDK学研字2023-1001)。

摘　　要：目的探索生长停滞特异基因1(GAS1)与乳腺癌患者免疫治疗及药物敏感性的关系。方法利用TCGA数据库数据分析GAS1在乳腺组织中的表达情况及与临床病理特征之间的关系;GSEA富集分析探索GAS1与基因集的关系;CIBERSORT法分析22种免疫细胞的比例,并探索GAS1与免疫浸润细胞的关系;使用TCIA数据库评估GAS1的表达与CTLA4和PD1免疫表型评分的关系;利用GDSC数据库探索GAS1与不同药物敏感性的关系。利用2016年1月—2017年12月在哈尔滨医科大学附属肿瘤医院乳腺外科接受手术治疗的乳腺癌患者的96例癌组织及33例癌旁组织资料进行GAS1免疫组织化学染色验证。结果TCGA数据库结果表明,GAS1在乳腺癌组织中的表达量显著低于正常乳腺组织(P<0.001),GAS1表达水平与年龄存在相关性(P=0.040)。包括细胞黏附分子在内的多种通路主要在GAS1高表达组中富集。GAS1高、低表达组间CD8 T细胞、滤泡辅助T细胞及巨噬细胞M1差异有统计学意义(P<0.05)。GAS1高表达组ips_ctla4_neg_pd1_pos及ips_ctla4_pos_pd1_pos评分高于低表达组,差异有统计学意义(P<0.05)。GAS1高表达组多西他赛、表阿霉素、顺铂、氟维司群、紫杉醇、帕博西利和奥拉帕利的IC 50值小于低表达组,差异有统计学意义(P<0.05)。临床样本中,乳腺癌患者癌组织中GAS1高表达者比例显著低于癌旁组织,差异有统计学意义(P<0.001)。GAS1的表达水平与分子分型是否为三阴性、组织学分级和CK5/6状态有关(P<0.05)。结论GAS1高表达的乳腺癌患者对免疫治疗药物PD1及部分常见化疗药物更为敏感,可以使用GAS1预测乳腺癌患者对这些药物的敏感性。Objective The aim of this study was to explore the relationship between growth arrest specific gene 1(GAS1),immunotherapy and drug sensitivity in breast cancer patients.Methods The expression of GAS1 in breast tissues and its relationship with clinicopathological features were analyzed using TCGA database data.The relationship between GAS1 and gene set was explored by GSEA enrichment analysis.The CIBERSORT method was used to analyze the proportion of 22 types of immune cells and explore the relationship between GAS1 and immune infiltrating cells.The TCIA database was used to evaluate the relationship between GAS1 expression and the CTLA4 and PD1 immunophenotypic scores.The GDSC database was used to explore the relationship between GAS1 and different drug sensitivities.The data of 96 cases of breast cancer patients and 33 cases of adjacent tissues from January 2016 to December 2017 in the department of Breast Surgery,Cancer Hospital of Harbin Medical University were used for GAS1 immunohistochemical staining verification.Results The results of TCGA database showed that the expression of GAS1 in breast cancer tissues was significantly lower than that in breast adjacent tissues(P<0.001),and the level of GAS1 was correlated with age(P=0.040).Multiple pathways,including cell adhesion molecules,were mainly enriched in the high expression group of GAS1.There were significant differences in CD8 T cells,follicular helper T cells and macrophage M1 between the high and low expression groups of GAS1(P<0.05).The ips_ctla4_neg_pd1_pos and ips_ctla4_pos_pd1_pos scores in the high expression group of GAS1 were higher than those of the low expression group of GAS1,and the difference was statistically significant(P<0.05).The IC 50 values of docetaxel,epirubicin,cisplatin,fluvestrant,paclitaxel,palbociclib,and olaparib in the high expression group of GAS1 were lower than those in the low expression group,and the difference was statistically significant(P<0.05).In clinical samples,the proportion of high GAS1 expression in cancer tis

关 键 词：生长停滞特异基因1 乳腺癌 免疫治疗 药物敏感性 

分 类 号：R737.9[医药卫生—肿瘤]