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基于炎症相关基因的肺腺癌分子亚型特征及预后模型的建立

Molecular subtype characteristics and development of prognostic model based on inflammation-related gene in lung adenocarcinoma.

作者信息

Hu Xuelei, Jiang Tengfei, Wang Jinxiang

机构信息

Department of Thoracic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China.

Medical Laboratory Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China.

出版信息

Discov Oncol. 2025 May 23;16(1):875. doi: 10.1007/s12672-025-02513-3.

DOI:10.1007/s12672-025-02513-3
PMID:40407957
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12102027/
Abstract

As one of the leading causes of death worldwide, lung adenocarcinoma (LUAD) currently lacks satisfactory treatment outcomes. The inflammatory process, closely associated with the formation of the tumor microenvironment and immune evasion, plays a crucial role in LUAD development. This study utilized data from public databases to analyze inflammation-related genes (INF) associated with prognosis in LUAD. Based on differentially expressed INF, molecular subtypes of LUAD were identified. Subsequently, a novel INF scoring system was developed to establish a prognostic model for LUAD patients, assessing its independence and reliability. Comprehensive evaluations, including immune microenvironment infiltration features, somatic mutation characteristics, and differences in immune therapy responsiveness, were conducted to characterize the prognostic model associated with INF. We further selected MMP14 from the screened INF targets for further in vitro experiments. Experiments such as western blot, qRT-PCR, colony-forming assay and Transwell assay confirmed that downregulation of MMP14 could inhibit the cloning, proliferation and invasion of lung cancer cells, thus confirming the results of bioinformatics. Our findings provide evidence from a new perspective on the role of inflammation in LUAD and offer new insights for clinical precision and personalized therapy.

摘要

作为全球主要死因之一,肺腺癌(LUAD)目前缺乏令人满意的治疗效果。炎症过程与肿瘤微环境的形成和免疫逃逸密切相关,在肺腺癌的发展中起着关键作用。本研究利用公共数据库的数据,分析与肺腺癌预后相关的炎症相关基因(INF)。基于差异表达的INF,确定了肺腺癌的分子亚型。随后,开发了一种新的INF评分系统,为肺腺癌患者建立预后模型,并评估其独立性和可靠性。进行了包括免疫微环境浸润特征、体细胞突变特征以及免疫治疗反应性差异在内的综合评估,以表征与INF相关的预后模型。我们进一步从筛选出的INF靶点中选择MMP14进行进一步的体外实验。蛋白质免疫印迹、实时荧光定量PCR、集落形成试验和Transwell试验等实验证实,MMP14的下调可抑制肺癌细胞的克隆、增殖和侵袭,从而证实了生物信息学的结果。我们的研究结果从新的角度为炎症在肺腺癌中的作用提供了证据,并为临床精准和个性化治疗提供了新的见解。

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本文引用的文献

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PPAR-γ/NF-kB/AQP3 axis in M2 macrophage orchestrates lung adenocarcinoma progression by upregulating IL-6.PPAR-γ/NF-kB/AQP3 轴通过上调 IL-6 调控 M2 巨噬细胞促进肺腺癌进展。
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