Obesity promotes lipid accumulation in lymph node metastasis of gastric cancer: a retrospective case‒control study
Jian Xiao, Kuan Shen, Kanghui Liu, Yuanhang Wang, Hao Fan, Quan Cheng, Xinyi Zhou, Li Hu, Gang Wang, Zekuan Xu, Li Yang
Abstract
BACKGROUND: The connection between obesity, lipid accumulation, and lymph node metastasis (LNM) in gastric cancer (GC) is unclear. METHODS: The association of body mass index (BMI) and serum lipid levels with LNM was measured by calculating the odds ratio (OR) and 95% confidence interval (CI) in 1,058 eligible GC patients with a mean age of 61.4 years. Meanwhile, differentially expressed genes (DEGs) were identified between lymph node metastasis-positive (N +) and -negative (N0) groups using public RNA-seq data. Neutral lipids in human GC samples were detected by Oil red O staining. The expression of cluster of differentiation 36 (CD36), fatty acid synthase (FASN), and lipoprotein lipase (LPL) was detected by immunohistochemistry (IHC) and quantitative real-time PCR. RESULTS: Compared with normal-weight patients, overweight (OR = 2.02, 95% CI = 1.26-3.23) and obese (OR = 1.83, 95% CI = 1.15-2.91) patients showed increased ORs for LNM. However, no significant results were obtained for serum lipids in the multivariable-adjusted model (P > 0.05). Subgroup analysis suggested that increased low-density lipoprotein cholesterol was a risk factor in females (OR = 1.27, 95% CI = 1.02-1.59). Functional enrichment analysis of DEGs revealed a connection between lipid metabolism and LNM. Meanwhile, lipid staining showed a mass of lipids in obese N + tumor samples, and IHC analysis indicated an increase in LPL and CD36 expression in N + cases, implying a crucial role for exogenous lipid supply in LNM. CONCLUSIONS: High BMI significantly increases the risk of LNM in GC and promotes lipid accumulation in GC cells in LNM.