title: Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system.
abstract: Vascular endothelial growth factor (VEGF) reportedly has an important role in the progression of malignant neoplasms and has been reported to induce myeloid-derived suppressor cells (MDSCs) that appear in cancer and inflammation. In the present study, serum concentrations of VEGF were measured in patients with digestive system cancer and the correlations with nutritional damage, immune suppression and systemic inflammation were analyzed. A significant increase in VEGF serum levels was observed in patients with esophageal, gastric and colorectal cancers compared with healthy volunteers. Levels of VEGF were inversely correlated with the serum concentrations of albumin, prealbumin and retinol-binding protein. The serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC counts. VEGF levels were also correlated with neutrophil and neutrophil/lymphocyte counts and inversely correlated with lymphocyte count. Serum VEGF levels were divided at a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. The stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels and MDSC counts tended to be higher in this group. These results demonstrated that increased production of VEGF was correlated with systemic inflammation, nutritional impairment and the inhibition of cell-mediated immunity involving MDSCs.
authors.affiliation: Departments of Organ Regulatory Surgery, Fukushima 960-1295;
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakamura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibata
authors.forename: Kenji
authors.initials: K
authors.lastname: Gonda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yazawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Anazawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohto
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Tomita
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
keywords: cachexia; colorectal cancer; gastric cancer; immunosuppression; myeloid-derived suppressor cells; systemic inflammation; vascular endothelial growth factor