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基于细胞焦亡信号构建肺癌腺癌的新型分子亚型和11基因特征。

Constructing novel molecular subtypes and an 11-gene signature based on pyroptosis signaling for lung adenocarcinoma.

作者信息

Li Lu, He Qing, Tao Zhenchao, Zhang Rui, Cui Yayun, Qian Liting

机构信息

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230031, Anhui, China.

Department of Oncology, The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei 230601, Anhui, China.

出版信息

Am J Cancer Res. 2022 Jul 15;12(7):3051-3066. eCollection 2022.

PMID:35968341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9360228/
Abstract

Pyroptosis plays important roles in various cancers. In this study, we focused on lung adenocarcinoma (LUAD) and aimed to develop new molecular subtypes based on pyroptosis signaling. Pyroptosis-related genes were used as a basis to classify molecular subtypes through unsupervised consensus clustering. Gene set enrichment analysis was performed to characterize tumor microenvironment (TME) and functional pathways. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify prognostic genes for establishing a prognostic model. Three molecular subtypes were established with distinct overall survival, TME and enriched pathways. C3 subtype had the longest survival and the highest immune infiltration. 11 prognostic genes were screened to build a prognostic signature for predicting LUAD prognosis. This study emphasized the important role of pyroptosis in LUAD development. Pyroptosis was considered to play critical roles in regulating TME. Moreover, the 11-gene signature could serve as an indicator for predicting LUAD prognosis, and was potential targets for developing targeted drugs.

摘要

细胞焦亡在多种癌症中发挥着重要作用。在本研究中,我们聚焦于肺腺癌(LUAD),旨在基于细胞焦亡信号开发新的分子亚型。以细胞焦亡相关基因作为基础,通过无监督一致性聚类对分子亚型进行分类。进行基因集富集分析以表征肿瘤微环境(TME)和功能通路。进行单变量Cox回归和最小绝对收缩和选择算子(LASSO)分析以鉴定用于建立预后模型的预后基因。建立了三种具有不同总生存期、TME和富集通路的分子亚型。C3亚型生存期最长且免疫浸润最高。筛选出11个预后基因以构建预测LUAD预后的预后特征。本研究强调了细胞焦亡在LUAD发生发展中的重要作用。细胞焦亡被认为在调节TME中起关键作用。此外,11基因特征可作为预测LUAD预后的指标,并且是开发靶向药物的潜在靶点。

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本文引用的文献

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Pyroptosis, a new bridge to tumor immunity.细胞焦亡,肿瘤免疫的新桥梁。
Cancer Sci. 2021 Oct;112(10):3979-3994. doi: 10.1111/cas.15059. Epub 2021 Aug 10.
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020:全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
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PD-L1 controls cancer pyroptosis.程序性死亡受体配体1(PD-L1)控制癌症细胞焦亡。
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PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.PD-L1 介导体细胞焦亡的 gasdermin C 表达将细胞凋亡转换为细胞焦亡,并促进肿瘤坏死。
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Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells.细胞毒性淋巴细胞中的颗粒酶 A 裂解 GSDMB 以在靶细胞中引发细胞焦亡。
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