Visceral-to-subcutaneous fat ratio independently predicts the prognosis of locally advanced gastric cancer----- highlighting the role of adiponectin receptors and PPARα, β/ δ, ɤ

Background: Results of computed tomography body composition (CTBC) predicting long-term outcomes of gastric cancer have been mixed and the plausible mechanism remains elusive. Methods: We retrospectively enrolled a cohort of stage III gastric cancer who had undergone curative-intent gastrectomy. Clinicopathological variables, preoperative CTBC including abdominal muscle, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and nutritional and inflammatory index were taken together to construct prognostic analysis. In vitro tests using co-culture system of gastric cancer cell lines and visceral adipocytes were conducted. Results: A total of 191 eligible patients were enrolled. By multivariate analysis, SAT and VAT/ SAT ratio were prognostic factors of disease-free survival, while sarcopenia was not. SAT remained as a prognostic factor of overall survival. SAT index was positively correlated with prognostic nutritional index, while VAT HU was positively correlated with platelet-to-lymphocyte ratio. Expression of adiponectin receptor 1 and 2 (AdipoR1, R2), and peroxisome proliferator-activated receptor (PPAR) α, β/δ, ɤ of patients with higher VAT/SAT ratio were decreased as compared to those with lower VAT/SAT ratio. Proliferation of gastric cancer cells co-cultured with adipocytes was increased by 50–100% and accompanied by down-regulation of mRNAs of AdipoR1, 2, PPARα, β/δ, ɤ, and pro-apoptotic genes, as compared to their controls. Conclusion: SAT and VAT played exactly opposite prognostic roles of locally advanced gastric cancers, which might work through modulation of AdipoR1, 2 and PPARα, β/δ, ɤ. Preoperative CTBC, supplementary to classic TNM system, helps clinicians tailor individualized adjuvant therapy and/or nutritional support.