为了了解高脂肪饮食（HFD）对肺癌进展和开发生物标志物的影响，我们在这里使用了诱导突变表皮生长因子受体（EGFR）驱动的肺癌转基因小鼠模型，该模型喂食常规饮食（RD）或高脂肪饮食（HFD）。结果显示，与RD肺癌组（LC-RD组）相比，HFD肺癌组（LC-HFD组）表现出显着的肿瘤形成和恶化，例如更高的EGFR活性和增殖标志物表达。肺组织的转录组分析显示，LC-HFD组中显着变化的基因在免疫相关信号通路中高度富集，表明HFD改变了促进肿瘤生长的免疫微环境。经过细胞因子和脂肪因子阵列结合元数据库软件的综合分析，C反应蛋白（CRP）成为LC-HFD组中最有可能的潜在候选者，表现出肺癌增殖和转移增强；这已被实验证实。我们的结果表明，HFD 可以将肿瘤生长环境转变为免疫相关的促肿瘤微环境，并证明 CRP 在该微环境中具有促进肺癌发展的作用。© 2023。由 The Company of Biologies Ltd 出版。

To understand the effects of a high-fat diet (HFD) on lung cancer progression and developing biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed with a regular diet (RD) or high-fat diet (HFD). The results displayed the HFD lung cancer group (LC-HFD group) exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer group (LC-RD group). The transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that HFD alters the immune microenvironment for promoting tumor growth. Following cytokines and adipokines arrays combined with a comprehensive analysis using meta-database software, C-reactive protein (CRP) emerged as the most likely potential candidate within the LC-HFD group, presenting enhanced lung cancer proliferation and metastasis; this was confirmed experimentally. Our results imply that HFD could turn the tumor growth environment into an immune-related pro-tumorigenic microenvironment and demonstrate that CRP has a role in promoting lung cancer development in this microenvironment.© 2023. Published by The Company of Biologists Ltd.