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食管癌免疫原性细胞死亡应用预测模型的建立与验证

Development and validation of immunogenic cell death-applied prediction model for esophageal carcinoma.

作者信息

Wen Yazhou, You Dongshan, Bai Yongkang, Cao Jing, Zhang Louqian, Xia Xiaoyang

机构信息

Department of Anesthesiology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital Nanjing, Jiangsu, China.

Department of Medical Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University/The First People's Hospital of Chuzhou Chuzhou, Anhui, China.

出版信息

Am J Cancer Res. 2023 May 15;13(5):2104-2115. eCollection 2023.

Abstract

Evidence suggests that immunogenic cell death (ICD) releases cancer antigens that promote cytotoxic T-cell responses, potentially improving immunotherapy. However, the relationship between ICDs and esophageal cancer (EC) remains unclear. This study aimed to determine the role of ICDs in EC and to construct an ICD-based prognostic panel. RNA-seq data of EC and the corresponding clinical information were downloaded from the UCSC-Xena platform to explore the association between ICD gene expression and EC prognosis. The GSE53625 dataset was used to validate the proposed model. Differentially expressed genes (DEGs) between different molecular subtypes were identified to construct a new ICD-related prognosis panel and generate molecular subtypes using ConsensusClusterPlus. We created a prognostic profile based on the ICD and a nomogram based on the risk score. Compared with normal samples, ICD gene expression of malignant samples were significantly increased. 161 patients with EC were successfully divided into three subtypes (SubA, SubB, and SubC). Patients with EC in the SubC group had the best survival and lowest ICD score, whereas patients in the SubB group had the worst prognosis. DEGs between subtypes were evaluated, and risk panels were established using LASSO-Cox regression analysis. The prognosis of low-risk patients was significantly better than that of high-risk patients in both cohorts. The area under the curve of the receiver operating characteristic curve indicated that the risk group had a good prognostic value. Our study identified the molecular subtypes of EC and ICD-based prognostic signatures. Our three-gene risk panel could serve as a biomarker for effectively assessing the prognostic risk of patients with EC.

摘要

有证据表明,免疫原性细胞死亡(ICD)会释放促进细胞毒性T细胞反应的癌症抗原,这可能会改善免疫治疗。然而,ICD与食管癌(EC)之间的关系仍不清楚。本研究旨在确定ICD在EC中的作用,并构建基于ICD的预后模型。从UCSC-Xena平台下载EC的RNA测序数据及相应临床信息,以探索ICD基因表达与EC预后之间的关联。使用GSE53625数据集验证所提出的模型。鉴定不同分子亚型之间的差异表达基因(DEG),以构建新的ICD相关预后模型,并使用ConsensusClusterPlus生成分子亚型。我们基于ICD创建了一个预后特征,并基于风险评分创建了一个列线图。与正常样本相比,恶性样本的ICD基因表达显著增加。161例EC患者成功分为三个亚型(SubA、SubB和SubC)。SubC组的EC患者生存最佳且ICD评分最低,而SubB组患者预后最差。评估亚型之间的DEG,并使用LASSO-Cox回归分析建立风险模型。在两个队列中,低风险患者的预后均显著优于高风险患者。受试者工作特征曲线下面积表明风险组具有良好的预后价值。我们的研究确定了EC的分子亚型和基于ICD的预后特征。我们的三基因风险模型可作为有效评估EC患者预后风险的生物标志物。

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Targeting immunogenic cell death in cancer.针对癌症的免疫原性细胞死亡。
Mol Oncol. 2020 Dec;14(12):2994-3006. doi: 10.1002/1878-0261.12851. Epub 2020 Dec 1.
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