Abstract
BACKGROUND: B7-H4 is a member of the B7 family of immune-regulatory ligands and is considered to be a negative regulator of the immune response. We investigated the clinical significance of serum soluble B7-H4 in patients with non-metastatic clear cell renal cell carcinoma. METHODS: We analyzed 108 patients in whom non-metastatic clear cell renal cancer was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum soluble B7-H4 level using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and evaluated the association between the peripheral blood neutrophil count and sB7-H4 as well as the utility of soluble B7-H4 as a prognostic biomarker for clear cell renal cancer. The Cox proportional hazards regression model was used to assess the PFS and OS with the soluble B7-H4 level. RESULTS: We detected high levels of soluble B7-H4 in the sera of 56% of patients with non-metastatic clear cell renal cell carcinoma versus only 10% of healthy donors. Elevated soluble B7-H4 levels were associated with changes in an elevated peripheral blood neutrophil count. The increase of soluble B7-H4 also was significantly associated with poor PFS and OS. Multivariate analysis showed that the elevation of the soluble B7-H4 level was an independent prognostic factor for PFS and OS. CONCLUSIONS: Our data suggest that the association between serum soluble B7-H4 and peripheral blood neutrophil count, as well as the evaluation of serum soluble B7-H4 expression is a useful tool for predicting the prognosis of patients with non-metastatic clear cell renal cell carcinoma.