MIP-1γ and SDF-1α Confer to High-Fat Diet Enhanced Lung Adenocarcinoma Progression

Abstract

Background: Obesity is a serious health problem worldwide. The correlation of obesity and chronic diseases and cancer been well-documented. Although obesity can promote cancer progression, the mechanism is largely unknown and thus an ideal animal model is required especially in lung cancer. Methods: We utilized an inducible mutant EGFR driven lung cancer transgenic mouse to address this issue. Mice with lung cancer induction were fed with regular diet (RD) or high-fat diet (HFD) followed by tumor burden evaluation. Lung tissues were harvested for whole-genome transcriptomic, gene enrichment analysis, and cytokine array for potential signatures identification. Findings: Mice with HFD treatments had significant body weight increments compared with RD treatments (p 2-fold, p<0.05). NF-κB was a core transcription factor in the regulatory network to mediate HFD-induced signaling based on pathway analysis. MIP-1γ and SDF-1α were most two cytokines conferred to HFD-enhanced progression. They also highly correlated to overall survival in patients with lung adenocarcinoma according to online database analysis. Interpretation: We firstly provided a whole-genome transcriptomic profiling, potential regulatory networks, and cytokine signatures related to HFD-enhanced lung cancer progression. This is potential for disease monitoring, diet management, and clinical outcome prediction. Funding Statement: This work was supported by grants from the Ministry of Science and Technology (MOST), Taiwan (No. MOST105-2628-B-002-051-MY3, MOST104-2320-B-002-030, MOST101-2320-B-002-048, to Kang-Yi Su). Declaration of Interests: The authors declared that they have no conflict of interest. Ethics Approval Statement: All animal studies were carried in the AAALac accredited animal center of National Taiwan University Medical College and approved by the Institutional Animal Care and Use Committee (IACUC) with No.20140453.