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鉴定肺腺癌中与 PANoptosis 相关的预后基因,并基于生物信息学分析开发预测模型。

Identifying prognostic genes related PANoptosis in lung adenocarcinoma and developing prediction model based on bioinformatics analysis.

机构信息

Oncology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.

College of Pharmacy, Hunan Traditional Chinese Medical College, Zhuzhou, China.

出版信息

Sci Rep. 2023 Oct 20;13(1):17956. doi: 10.1038/s41598-023-45005-6.

DOI:10.1038/s41598-023-45005-6
PMID:37864090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10589340/
Abstract

Cell death-related genes indicate prognosis in cancer patients. PANoptosis is a newly observed form of cell death that researchers have linked to cancer cell death and antitumor immunity. Even so, its significance in lung adenocarcinomas (LUADs) has yet to be elucidated. We extracted and analyzed data on mRNA gene expression and clinical information from public databases in a systematic manner. These data were utilized to construct a reliable risk prediction model for six regulators of PANoptosis. The Gene Expression Omnibus (GEO) database validated six genes with risk characteristics. The prognosis of LUAD patients could be accurately estimated by the six-gene-based model: NLR family CARD domain-containing protein 4 (NLRC4), FAS-associated death domain protein (FADD), Tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD), Receptor-interacting serine/threonine-protein kinase 1 (RIPK1), Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2), and Mixed lineage kinase domain-like protein (MLKL). Group of higher risk and Cluster 2 indicated a poor prognosis as well as the reduced expression of immune infiltrate molecules and human leukocyte antigen. Distinct expression of PANoptosis-related genes (PRGs) in lung cancer cells was verified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, we evaluated the relationship between PRGs and somatic mutations, tumor immune dysfunction exclusion, tumor stemness indices, and immune infiltration. Using the risk signature, we conducted analyses including nomogram construction, stratification, prediction of small-molecule drug response, somatic mutations, and chemotherapeutic response.

摘要

细胞死亡相关基因预示癌症患者的预后。PANoptosis 是一种新观察到的细胞死亡形式,研究人员将其与癌细胞死亡和抗肿瘤免疫联系起来。即便如此,其在肺腺癌(LUAD)中的意义仍有待阐明。我们系统地从公共数据库中提取和分析了 mRNA 基因表达和临床信息的数据。这些数据被用于构建一个可靠的 PANoptosis 六种调节剂的风险预测模型。基因表达综合数据库(GEO)验证了具有风险特征的六种基因。基于这六种基因的模型可以准确估计 LUAD 患者的预后:NLR 家族 CARD 结构域蛋白 4(NLRC4)、FAS 相关死亡结构域蛋白(FADD)、肿瘤坏死因子受体 1 相关死亡结构域蛋白(TRADD)、受体相互作用丝氨酸/苏氨酸蛋白激酶 1(RIPK1)、脯氨酸-丝氨酸-苏氨酸磷酸酶相互作用蛋白 2(PSTPIP2)和混合谱系激酶结构域样蛋白(MLKL)。高风险组和聚类 2 表明预后不良,并且免疫浸润分子和人类白细胞抗原的表达降低。使用定量逆转录聚合酶链反应(qRT-PCR)验证了肺癌细胞中 PANoptosis 相关基因(PRGs)的不同表达。此外,我们评估了 PRGs 与体细胞突变、肿瘤免疫功能障碍排除、肿瘤干性指数和免疫浸润之间的关系。使用风险特征,我们进行了分析,包括列线图构建、分层、小分子药物反应预测、体细胞突变和化疗反应预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/a030c3ea61d9/41598_2023_45005_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/37815c743d26/41598_2023_45005_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/1782f4bf052f/41598_2023_45005_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/1f5a70366ab4/41598_2023_45005_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/20122a372010/41598_2023_45005_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/4f1a659aad52/41598_2023_45005_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/a030c3ea61d9/41598_2023_45005_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/37815c743d26/41598_2023_45005_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/80fa272d7a57/41598_2023_45005_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/d3585800a66d/41598_2023_45005_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/aee9fb25ec16/41598_2023_45005_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/1782f4bf052f/41598_2023_45005_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/1f5a70366ab4/41598_2023_45005_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/20122a372010/41598_2023_45005_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/4f1a659aad52/41598_2023_45005_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f578/10589340/a030c3ea61d9/41598_2023_45005_Fig9_HTML.jpg

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Construction of the model for predicting prognosis by key genes regulating EGFR-TKI resistance.通过调控EGFR-TKI耐药的关键基因构建预后预测模型。
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The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest.
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