Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy.

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Shasha Cao, Shumin Lun, Lijuan Duan, Zhaowei Gao, Xiaoxiao Wang, Yutong Li, Yaowen Zhang
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引用次数: 0

Abstract

Summary: Calmodulin (CALM) has a bearing on the prognosis of various cancers. However, the prognostic value of CALM in esophageal squamous cell carcinoma (ESCC) remains unelucidated. Differentially expressed genes (DEGs) were screened between normal and tumor groups of TCGA-ESCC sets. The intersection of DEGs with calmodulin-related genes (CRGs) yielded differentially expressed CRGs (DE-CRGs). A prognostic model was established using LASSO Cox regression analysis and multivariate Cox regression analysis. qPCR validated the expression of prognostic feature genes. Analysis of gene expression patterns of different cellular clusters was based on single-cell sequencing data. Lastly, GSEA enrichment, immune infiltration, mutational profiling, drug sensitivity, and molecular docking as well as cellular thermal shift assay (CETSA) were conducted for ESCC patients. A prognosis model with excellent predictive capability was created based on 4 feature genes (ATP2B3, CALB1, KCNQ1, and MYO1G). The qPCR results demonstrated that ATP2B3 and KCNQ1 were significantly downregulated in human ESCC cells, whereas CALB1 and MYO1G were upregulated (P<0.05). Single-cell analysis uncovered that MYO1G and KCNQ1 were mainly expressed in different cell clusters. Furthermore, this risk model was strongly associated with functional pathway enrichment, immune cell infiltration, and somatic mutations. We also identified AZD-8055 may be potential therapy for ESCC patients. The CETSA experiment demonstrated the existence of a favorable binding thermal stability between AZD-8055 and MYO1G. This research may identify potential biomarkers for predicting the prognosis of ESCC patients.

利用钙调素相关基因构建食管鳞状细胞癌预后模型,综合分析单细胞免疫特性和药物疗效。
摘要:钙调素(Calmodulin, CALM)与多种癌症的预后有关。然而,CALM在食管鳞状细胞癌(ESCC)中的预后价值尚不清楚。筛选TCGA-ESCC正常组与肿瘤组之间的差异表达基因(DEGs)。DEGs与钙调素相关基因(calmodulin-related genes, CRGs)的交叉产生差异表达的CRGs (DE-CRGs)。采用LASSO Cox回归分析和多变量Cox回归分析建立预后模型。qPCR验证了预后特征基因的表达。不同细胞簇的基因表达模式分析基于单细胞测序数据。最后,对ESCC患者进行GSEA富集、免疫浸润、突变谱分析、药物敏感性、分子对接以及细胞热移测定(CETSA)。基于4个特征基因(ATP2B3、CALB1、KCNQ1、MYO1G)建立了具有较好预测能力的预后模型。qPCR结果显示,ATP2B3和KCNQ1在人ESCC细胞中显著下调,而CALB1和MYO1G上调(P
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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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