The significance of vascular endothelial growth factor and systemic inflammatory reaction in bladder cancer patients

Bladder cancer (BCa) is the most frequently diagnosed malignancy of the urinary system and is characterized by a multifactorial etiology. Multiple growth factors have been implicated in BCa progression. This cross-sectional study investigated whether the pro-angiogenic factors angiopoietin-like 4 (ANGPTL4), insulin-like growth factor 1 (IGF-1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) could differentiate BCa patients according to the degree of systemic inflammation. Based on histopathological examination, 101 participants were enrolled and divided into a cancer group (CG; n = 69), and a non-cancer group (NCG; n = 32), comprising patients who were not diagnosed with BCa following histopathological evaluation. Healthy control was also recruited from Blood Donor Repository ( n = 34). The control group was younger (median min-max years old; CG: 71 (48–92); NCG: 70 (26–86); control: 43 (28–61); p < 0.0001) and had a lower body mass index (BMI) compared to the CG and NCG groups (median min-max kg/m 2 ; CG: 27 (21–43); NCG: 27 (19–37); control: 21 (20−31); p < 0.0001). The CG was stratified by median C-reactive protein (CRP) level (4.53 μg/mL) and further analyzed. Regardless of CRP level, patients in both the CG and NCG groups had higher concentrations of all assessed proangiogenic and proinflammatory markers than healthy controls. Individuals with BCa, regardless of CRP level, were more likely to be smokers compared with NCG ( p < 0.001), which was confirmed in a multivariate analysis pointing to smoking as the only variable that significantly differentiated the CG from the NCG (OR = 3.78, 95% CI: 1.36–10.54, p = 0.0109). No significant differences in tumor grade or TNM classification were observed between the low-CRP and high-CRP subgroups. Analysis of inflammatory parameters revealed significant differences in CRP concentrations alone. The high-CRP CG subgroup exhibited significantly higher CRP levels compared with both the low-CRP CG subgroup and the NCG ( p < 0.0001). Analysis of proangiogenic markers revealed differences only in VEGF. No significant differences were observed for ANGPTL4, IGF-1, and FGF21, as well as in the counts of leucocytes and platelets.VEGF concentrations differed significantly between subgroups and were highest in the high-CRP CG subgroup compared with the low-CRP CG subgroup and the NCG (median pg/mL: 186.7 vs. 120.5 vs. 120.6, respectively; p = 0.0330). Receiver operating characteristic (ROC) curve analysis of VEGF concentrations showed modest discriminative ability between CG and NCG, with an area under the curve (AUC) of 0.624 (95% CI: 0.529–0.719; p = 0.013). In the CG, multivariable linear regression showed that CRP was independently associated with higher VEGF levels after adjustment for smoking, tumor stage, age, sex, and BMI (β coefficient [95% CI) 0.302 [0.078;0.526]; p = 0.009), corresponding to an approximately 23.3% increase in VEGF for each twofold increase in CRP. Conclusion: These findings indicate that systemic inflammation, reflected by CRP levels, is independently associated with higher VEGF concentrations in BCa patients, supporting a potential link between inflammation and tumor-related angiogenesis.