基于生物信息学分析JCHAIN在乳腺癌远处转移中的预后价值  

The prognostic value of JCHAIN gene in breast cancer metastasis based on bioinformatics analysis

作　　者：刘洁[1] 方跃华[1] 陈勇[1] 王媛媛 王晓贤 林雨虹 周晓燕 LIU Jie;FANG Yuehua;CHEN Yong;WANG Yuanyuan;WANG Xiaoxian;LIN Yuhong;ZHOU Xiaoyan(Clinical Laboratory,Fuzhou First General Hospital Affiliated to Fujian Medical University,Fuzhou 350009,China)

机构地区：[1]福建医科大学附属福州市第一总医院检验科,福州350009

出　　处：《免疫学杂志》2024年第6期481-488,508,共9页Immunological Journal

基　　金：福建省自然科学基金项目(2023J011485);福州市科技计划项目(2021-S-171)。

摘　　要：目的基于生物信息学分析,探究JCHAIN在乳腺癌(breast cancer,BC)远处转移(distant metastasis,DM)中的预后价值及可能的调控机制。方法①TCGA数据库下BC转录组测序数据,筛选差异表达基因(DEGs),结合临床数据进一步筛选与肿瘤发生和转移相关的基因;②单因素Cox分析发现10个关键基因与OS显著相关,多因素Cox分析筛选出4个显著相关基因;③结合8种免疫浸润细胞亚型的分析算法,研究JCHAIN表达水平与肿瘤微环境中浸润细胞的亚型和各细胞成分占比的相关性;④利用抗癌药物敏感性基因组学(GDSC)数据库对不同JCHAIN表达水平的BC患者进行化疗药物敏感性分析;⑤通过双萤光素酶报告系统探究JCHAIN在发生DM的BC中低表达的可能机制。结果①根据筛选出的关键基因,成功构建了预后模型,并发现随着模型风险值的增加,JCHAIN、TUBA3D基因表达呈现下调趋势,而SPDYC、CRISP3基因表达上调;②发生DM的BC患者JCHAIN基因表达<未发生DM<正常组织;③临床结局中死亡组的JCHAIN表达量低于生存组,且随着疾病(分期)的进展或恶性程度的加深,JCHAIN的表达基本呈下降的趋势;④JCHAIN高表达组各免疫细胞数量普遍高于低表达组,如,在有预测B细胞和T细胞(CD4^(+)/CD8^(+))表达的6种算法中,均为JCHAIN高表达组高于低表达组;⑤基于GDSC数据库,JCHAIN表达水平可预测化疗药物敏感性,表达水平与药物敏感性呈正相关;⑥转录因子TWIST1(TW)重组质粒参与的实验组萤光素检测值低于TW重组质粒未参与的对照组。结论①确定JCHAIN、TUBA3D为BC的保护因素,而SPDYC、CRISP3为危险因素;②JCHAIN水平降低可能促进BC发生DM;③JCHAIN高表达可能促进各种免疫细胞浸润;④BC患者JCHAIN高表达对治疗药物敏感性高于低表达组;⑤转录因子TW可结合JCHAIN启动子序列,并呈负向调控。This study was performed to investigate the prognostic value of JCHAIN gene in the distant metastasis(DM)of breast cancer(BC)and its possible regulatory mechanism through bioinformatics analysis.TCGA database BC transcriptome sequencing data were grouped according to sample source,and LIMMA was used to identify differentially expressed genes(DEGs),and combined with clinical data,genes related to tumorigenesis and metastasis were further screened.Single-factor Cox analysis revealed that 10 key genes were significantly associated with OS,while multi-factor Cox analysis further filtered out 4 genes with significant correlation.The analysis algorithm of 8 immune infiltration cell subtypes were used to evaluate the correlation of JCHAIN expression level with the subtype of infiltrating cells and the proportion of each cellular component in the tumor microenvironment.the genome-wide drug sensitivity of anti-cancer drugs(GDSC)database was used to analyze the chemotherapy drug sensitivity of BC patients with different JCHAIN expression levels;dual-luciferase reporter system was used to explore the mechanism of low JCHAIN expression in BC with DM.Based on the screened key genes,a prognostic model was successfully constructed,and it was found that with the increase of model risk value,the gene expression of JCHAIN and TUBA3D showed a down-regulation trend,while the gene expression of SPDYC and CRISP3 was up-regulated.②The expression of gene JCHAIN in BC patients with DM was lower than those in patients without DM and normal controls.In clinical outcomes,the expression level of gene JCHAIN in the death group was lower than that in the survival group,and with the progression of the disease(stage)or the deepening of malignancy,the expression of gene JCHAIN basically showed a downward trend.The number of immune cells in the JCHAIN high expression group was generally higher than that in the low expression group.For example,among the six algorithms that predict the expression of B cells and T cells(CD4^(+)/CD8^(+)),the JCHAIN

关 键 词：乳腺癌 JCHAIN 远处转移 预后价值 生物信息学 

分 类 号：R739.5[医药卫生—肿瘤]