Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma

• Published in: PloS one 2018-07, Vol.13 (7), p.e0199719-e0199719
• Main Authors: Azuma, Takeshi, Sato, Yujiro, Ohno, Tetsukuni, Azuma, Miyuki, Kume, Haruki
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Aged, 80 and over; B7 antigen; Bioindicators; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - blood; Blood; Cancer; Carcinoma, Renal Cell - blood; Clear cell-type renal cell carcinoma; Enzyme-linked immunosorbent assay; Female; Gastric cancer; Gene expression; Hazard assessment; Health care facilities; Humans; Immune response; Immune system; Immunology; Kidney cancer; Kidney Neoplasms - blood; Lymphocytes; Male; Medical diagnosis; Medical prognosis; Medicine and Health Sciences; Melanoma; Metastases; Metastasis; Middle Aged; Multivariate analysis; Neutrophils; Patients; Peripheral blood; Prognosis; Regression analysis; Regression models; Renal cell carcinoma; Research and Analysis Methods; Statistical analysis; Stomach cancer; Urology; V-Set Domain-Containing T-Cell Activation Inhibitor 1 - blood
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0199719

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. 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. 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. 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.