High-fat diet triggers C-reactive protein secretion enhancing lung adenocarcinoma progression through immune microenvironment modulation.

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.