Plasma cytokines and angiogenic factors (CAFs) associated with risk of recurrence and tumor dependence in patients (pts) with nonmetastatic renal cell carcinoma (RCC).

Abstract

383 Background: Although recent years have brought great progress into understanding the pathogenesis of RCC and multiple promising biomarkers, no tumor tissue or blood-based test has yet been validated for clinical use. The main objectives of this exploratory analysis were to identify CAFs predictive of recurrence in RCC pts, and to gain insight into tumor dependency of individual factors by comparing CAFs pre- and post-nephrectomy (Nx). Methods: Plasma samples were obtained before and up to 1 year after Nx from pts with sporadic, non-metastatic renal masses suspicious for RCC (n=73). Upon Nx, 52 pts showed dominant clear cell histology and 11 non-clear cell; 10 pts had non-cancerous lesions. RCC pts were categorized by risk of relapse based on pathologic staging (pT1/pT2 as low-risk [LR], n=38; pT3/pT4 as high-risk [HR], n=25). Multiplex bead suspension arrays and ELISA were used to measure concentrations of 58 CAFs including angiogenesis and invasion mediators (VEGF, VEGF-C, soluble CAIX [sCA9], hepatocyte growth factor and transforming growth factor-b1, among others), and multiple inflammatory and/or immunomodulatory chemokines and interleukins (IL). t-test and Wilcoxon signed rank or rank-sum tests were respectively used to assess changes in CAFs between pre- and post-Nx or to compare CAFs between subgroups of pts. Results: Of 58 pre-Nx CAFs available in RCC pts, the concentrations of IL-8, granulocyte-colony stimulating factor, stromal cell-derived factor-1, and osteopontin, among others, were significantly higher in HR vs. LR-RCC (all P<0.01). In pts with clear cell RCC, sCA9 was also higher (P=0.004). A number of CAFs significantly decreased post-Nx, including sCA9, endoglin, and e-selectin, while others increased, such as stem cell factor, IL-12, and vascular cell adhesion molecule-1. The pre-Nx concentrations of e-selectin were lower in pts with eventual disease recurrence (P=0.008). Conclusions: We identified pre-Nx CAFs associated with risk for recurrence, and post-Nx changes related to the presence of the tumor in pts with non-metastatic RCC. If validated in a larger study, these CAFs could be used for risk stratification of RCC pts.