Abstract 1564: Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer

Abstract

Abstract Autoantibodies against intracellular tumor associated antigens (TAAs) are commonly found in various types of human cancers. Their utility in providing insights into tumor biology and as potential cancer biomarkers is well documented. In this study, serum autoantibodies to the Ras family small GTP binding protein (RalA) were detected by immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), and immunoblotting in 353 sera from patients with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and normal controls. Expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry. The cumulative positive rate of autoantibodies against RalA in PCa reached 18.4%, higher than that in sera with BPH (14.7%) and normal human sera (NHS) (2.25%, P<0.01). Twenty seven of 32 (84.4%) sera with positive OD values were consistently positive in immunoblots. The sensitivity and specificity of anti-RalA antibody in PCa detection was 18.4% and 97.8%, respectively. Representative PCa sera showed a cytoplasmic immunofluorescence staining pattern, with more intense staining in the perinuclear regions or partial staining in intracellular membrane. This pattern was similar to that produced by monoclonal RalA antibody. Strong expression of RalA was observed in 76.5% of prostate tumor tissues. Anti-RalA and PSA simultaneously used as diagnostic markers improved the sensitivity of PCa detection to 57.4%. In addition, the appearance of autoantibodies to RalA was assessed over time in the serially collected samples after surgery in cases. In all cancer patients with anti-RalA positive, autoantibodies were detected in 6 of 54 serial samples taken after surgery with a median lead time of 121 days (Interquartile Range, IQR 0-360). In conclusion, autoantibody to RalA might be a potential serological biomarker for the immunodiagnosis of early stage PCa. We are currently identifying additional novel TAAs targeted by serum autoantibodies in PCa by using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem-mass spectrometry (LC-MS/MS). The combination of RalA with PSA, and with other antigens in PCa-specific TAA arrays has the potential for significantly improving the sensitivity of early PCa detection and management in diverse populations. Key words: anti-RalA autoantibody; tumor-associated antigens (TAAs); cancer immunodiagnosis; prostate cancer Citation Format: jitian li, Liping Dai, Carlos A. Casiano, Jianying Zhang. Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1564. doi:10.1158/1538-7445.AM2015-1564