■据报道,肿瘤免疫微环境在肿瘤进展中起着至关重要的作用。然而,免疫细胞相关基因(IRGs)在食管鳞状细胞癌(ESCC)中的作用机制尚不清楚。
■TCGA-ESCC,通过公共数据库获得GSE23400、GSE26886、GSE75241和GSE196756数据集。首先,通过差异表达分析筛选出ESCC与GSE23400、GSE26886和GSE75241对照样品之间的差异表达基因(DEGs),并确定了重叠的DEG。应用GSE196756的单细胞转录组数据来探索可能参与ESCC调控的免疫细胞。然后,应用加权基因共表达网络分析筛选IRGs。接下来,差异表达的IRGs(DE-IRGs)通过重叠的IRGs和DEGs鉴定,并被纳入单变量考克斯,最小绝对收缩和选择运算符,和多变量Cox来获取预后相关基因,根据中位风险评分将ESCC样本分为高/低风险组.最后,分析预后模型在免疫治疗中的作用。
■通过重叠GSE26886中的3,915个DEG、GSE23400中的459个DEG和GSE75241中的1,641个DEG,总共产生了248个DEG。单细胞分析发现B细胞,树突状细胞,单核细胞,中性粒细胞,自然杀伤细胞,和T细胞参与ESCC的发展。此外,MEred,MEblack,MEpink,MEblue和MEbrown模块被认为是关键模块,因为它们与免疫细胞亚型的相关性最高。通过在关键模块中获取DEG和基因的交叉,总共产生了154个DE-IRG。此外,CTSC,ALOX12和RMND5B在ESCC中被鉴定为预后相关基因。显然,高危人群的排除和TIDE评分明显低于另一组,表明高危人群对免疫疗法的反应更敏感.
■通过生物信息学分析,我们确定了一个由IRGs(CTSC,ALOX12和RMND5B)在ESCC中,为ESCC的治疗和预后相关研究提供新的思路。
UNASSIGNED: It has been reported that tumor immune microenvironment performs a vital role in tumor progress. However, acting mechanism of immune cell related genes (IRGs) in esophageal squamous cell carcinoma (ESCC) is uncertain.
UNASSIGNED: TCGA-ESCC, GSE23400, GSE26886, GSE75241, and GSE196756 datasets were gained via public databases. First, differentially expressed genes (DEGs) between ESCC and control samples from GSE23400, GSE26886, and GSE75241 were screened out by differential expression analysis, and overlapping DEGs were identified. Single-cell transcriptome data of GSE196756 were applied to explore immune cells that might be involved in regulation of ESCC. Then, weighted gene co-expression network analysis was applied to screen IRGs. Next, differentially expressed IRGs (DE-IRGs) were identified by overlapping IRGs and DEGs, and were incorporated into univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox to acquire prognosis-related genes, and ESCC samples were grouped into high-/low-risk groups on the basis of median risk score. Finally, the role of prognosis model in immunotherapy was analyzed.
UNASSIGNED: Totally 248 DEGs were yielded by overlapping 3,915 DEGs in GSE26886, 459 DEGs in GSE23400, and 1,641 DEGs in GSE75241. Single-cell analysis found that B cells, dendritic cells, monocytes, neutrophils, natural killer cells, and T cells were involved in ESCC development. Besides, MEred, MEblack, MEpink, MEblue and MEbrown modules were considered as key modules because of their highest correlations with immune cell subtypes. A total of 154 DE-IRGs were yielded by taking intersection of DEGs and genes in key modules. Moreover, CTSC, ALOX12, and RMND5B were identified as prognosis-related genes in ESCC. Obviously, Exclusion and TIDE scores were notably lower in high-risk group than in the other one, indicating that high-risk group was more responsive to immunotherapy.
UNASSIGNED: Through bioinformatic analysis, we identified a prognosis model consisting of IRGs (CTSC, ALOX12, and RMND5B) in ESCC, providing new ideas for studies related to treatment and prognosis of ESCC.