Evaluation of soluble B7x as a serum marker in patients with clear cell renal cell carcinoma

Abstract

5052 Background: Discovered in 2003, B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum soluble B7x (sB7x) and investigated patients with RCC. Methods: We identified 101 patients who underwent nephrectomy for clear cell RCC between 2003 and 2007 and had preoperative serum available. Enzyme- linked immunosorbent assay for sB7x was then performed with a minimum detection level of 0.1ng/ml. We also obtained serum from 101 sex- matched blood donors within the same age range who served as controls. Results: Detectable levels of sB7x were present in 53 RCC patients compared with 18 controls (p<0.001) with median (range) concentrations of 14.4ng/ml (0.1–56.9) and 2.7ng/ml (0.2–37.1), respectively. Among the RCC patients, no significant clinical, laboratory, or pathologic associations were observed between patients positive versus negative for sB7x. However, among RCC patients with detectable sB7x, median levels were significantly higher for patients with a tumor thrombus (19.2 vs 6.6ng/ml; p=0.007), positive lymph nodes (41.3 vs 10.3ng/ml; p=0.018), and distant metastases at nephrectomy (43.3 vs 8.5ng/ml; p=0.002). Additionally, median sB7x levels for TNM stage I-IV RCC were 6.6, 10.3, 14.5, and 43.3ng/ml, respectively (p=0.012). Conclusions: In this first evaluation of sB7x in RCC, we demonstrate that RCC patients are more likely to have detectable sB7x compared with controls and higher sB7x levels are associated with advanced tumor stage. These early results warrant further investigation of this serum marker for potential diagnostic and prognostic purposes. No significant financial relationships to disclose.