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肺腺癌中细胞焦亡的基因组学和免疫学特征

Genomic and Immunological Characterization of Pyroptosis in Lung Adenocarcinoma.

作者信息

Song Yaobo, Qu Zhen, Feng Hu, Xu Long, Xiao Yajie, Zhao Zhikun, Wu Dongfang, Sun Chao, Fan Xinglong, Zhou Dongmei

机构信息

Department of Medical Oncology Ward, Yantaishan Hospital, Yantai 264001, China.

Department of Oncology, No. 970 Hospital, Yantai, 264001, China.

出版信息

J Oncol. 2022 Jul 27;2022:6905588. doi: 10.1155/2022/6905588. eCollection 2022.

Abstract

Pyroptosis is a programmed cell death that may either promote or hinder cancer growth under different circumstances. Pyroptosis-related genes (PRGs) could be a useful target for cancer therapy, and are uncommon in lung adenocarcinoma (LUAD). The expression profiles, mutation data and clinical information of LUAD patients were included in this study. A pyroptosis-related prognostic risk score (PPRS) model was constructed by performing Cox regression, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score LUAD patients. Somatic mutation and copy number variation (CNV), tumor immunity, and sensitivity to immunotherapy/chemotherapy were compared between different PPRS groups. Clinical parameters of LUAD were combined with PPRS to construct a decision tree and nomogram. Red module was highly positively correlated with pyroptosis. Seven genes (FCRLB, COTL1, GNG10, CASP4, DOK1, CCR2, and AQP8) were screened from the red module to construct a PPRS model. Significantly lower overall survival (OS), higher incidence of somatic mutation and CNV, elevated infiltration level of the immune cell together with increased probability of immune escape were observed in LUAD patients with higher PPRS, and were more sensitive to Cisplatin, Docetaxel, and Vinorelbine. We constructed a new PPRS model for patients with LUAD. The model might have clinical significance in the prediction of the prognosis of patients with LUAD and in the efficacy of chemotherapy and immunotherapy.

摘要

细胞焦亡是一种程序性细胞死亡,在不同情况下可能促进或阻碍癌症生长。细胞焦亡相关基因(PRGs)可能是癌症治疗的有用靶点,且在肺腺癌(LUAD)中并不常见。本研究纳入了LUAD患者的表达谱、突变数据和临床信息。通过进行Cox回归、加权基因共表达网络分析(WGCNA)和最小绝对收缩和选择算子(LASSO)分析来对LUAD患者进行评分,构建了一个细胞焦亡相关的预后风险评分(PPRS)模型。比较了不同PPRS组之间的体细胞突变和拷贝数变异(CNV)、肿瘤免疫以及对免疫治疗/化疗的敏感性。将LUAD的临床参数与PPRS相结合构建决策树和列线图。红色模块与细胞焦亡高度正相关。从红色模块中筛选出7个基因(FCRLB、COTL1、GNG10、CASP4、DOK1、CCR2和AQP8)构建PPRS模型。PPRS较高的LUAD患者总生存期(OS)显著降低、体细胞突变和CNV发生率较高、免疫细胞浸润水平升高以及免疫逃逸概率增加,并且对顺铂、多西他赛和长春瑞滨更敏感。我们为LUAD患者构建了一个新的PPRS模型。该模型可能在预测LUAD患者预后以及化疗和免疫治疗疗效方面具有临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/9348947/3f533d1fe4ee/JO2022-6905588.001.jpg

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