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利用钙调蛋白相关基因构建食管鳞状细胞癌预后模型,以全面分析单细胞免疫特征和药物疗效。

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.

作者信息

Cao Shasha, Lun Shumin, Duan Lijuan, Gao Zhaowei, Wang Xiaoxiao, Li Yutong, Zhang Yaowen

机构信息

Henan Medical Key Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang, China.

出版信息

J Immunother. 2025 Sep 1;48(7):244-257. doi: 10.1097/CJI.0000000000000561.

Abstract

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.

摘要

钙调蛋白(CALM)与多种癌症的预后相关。然而,CALM在食管鳞状细胞癌(ESCC)中的预后价值仍不明确。在TCGA-ESCC数据集的正常组和肿瘤组之间筛选差异表达基因(DEG)。将DEG与钙调蛋白相关基因(CRG)进行交集分析,得到差异表达的CRG(DE-CRG)。使用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。基于单细胞测序数据分析不同细胞簇的基因表达模式。最后,对ESCC患者进行基因集富集分析(GSEA)、免疫浸润、突变谱分析、药物敏感性、分子对接以及细胞热位移分析(CETSA)。基于4个特征基因(ATP2B3、CALB1、KCNQ1和MYO1G)创建了一个具有出色预测能力的预后模型。qPCR结果表明,ATP2B3和KCNQ1在人ESCC细胞中显著下调,而CALB1和MYO1G上调(P<0.05)。单细胞分析发现,MYO1G和KCNQ1主要在不同细胞簇中表达。此外,该风险模型与功能通路富集、免疫细胞浸润和体细胞突变密切相关。我们还确定AZD-8055可能是ESCC患者的潜在治疗药物。CETSA实验证明AZD-8055与MYO1G之间存在良好的结合热稳定性。本研究可能为预测ESCC患者的预后识别潜在的生物标志物。

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