Obesity promotes lipid accumulation in lymph node metastasis of gastric cancer: a retrospective case‒control study

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.

Keywords: Body mass index; Lipids; Lymphatic metastasis; Obesity; Stomach neoplasms.

Fig. 1

Identification and functional enrichment analysis of DEGs. a Volcano plot presentation of DEGs between N0 and N + patients from the TCGA cohort. b GO enrichment analysis of DEGs from the TCGA cohort. The part enclosed by the black box is the cellular components related to lipid metabolism. c Volcano plot showing DEGs from the GSE15459 cohort. d Dot plot showing the results of GO enrichment analysis of DEGs from the GSE15459 cohort

Fig. 2

Oil red O staining of lipids in human tissue samples. a Detection of lipids in human tissue samples by oil red O staining. Scale bar = 10 µm. Neutral lipids in tissues were dyed red. b Expression levels of CD36, LPL, FASN, and CPT1A in forty tumor tissues (N0 = 15, N +  = 25) by qRT‒PCR

Fig. 3

Expression levels of LPL, CD36, and FASN in GC samples. a Representative microscopic image of LPL, CD36, and FASN expression in tumor tissues, adjacent normal tissues, N + tumor samples, and N0 tumor samples. Scale bar = 10 µm. b Staining intensity of LPL, CD36, and FASN expression was calculated in all tumor samples (n = 25), normal tissues (n = 25), N + tumor samples (n = 10), and N0 samples (n = 15)