Abstract
Autoantibodies against intracellular tumor-associated antigens (TAAs) are commonly found in human cancers. In this study, we characterized the serum autoantibody response to the RalA, Ras-like GTPase, in patients with prostate cancer (PCa). The autoantibodies were detected by immunofluorescence assay in PCa cell lines, ELISA, and immunoblotting in 339 serum samples from patients with PCa and benign prostatic hyperplasia (BPH), and in normal human sera (NHS). The expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry (IHC) in tumor microarrays. The autoantibody level to RalA (median) in NHS was significantly lower than in PCa (0.053 vs 0.138; P < 0.001) and BPH (0.053 vs 0.132; P < 0.005) groups. The circulating anti-RalA autoantibody could distinguish PCa patients from normal individuals with the area under the receiver operating characteristic (ROC) curve (AUC) performing at 0.861, with sensitivity of 52.9% and specificity of 91.0%. Elevation in serum immunoreactivity was observed in PCa patients after radical prostatectomy. The combined use of both anti-RalA autoantibody and PSA showed a significantly higher discriminatory ability compared with either of those markers alone. RalA protein expression was detected by IHC in 85.3% of tumor tissues from PCa patients, but without significant difference compared to BPH or normal control tissues. Together, our study shows the additional benefits of anti-RalA autoantibody as a potential serological biomarker for PCa, particularly in patients with normal PSA, and further demonstrate the utility of biomarker combinations in the immunodiagnosis of PCa.
Highlights
Prostate cancer (PCa) is the most frequently diagnosed cancer (28%) and the second leading cause of male cancer deaths (10%) in the U.S, with an estimated 220,800 cases and 27,540 deaths in 2015 [1]
The receiver operating characteristic (ROC) curves discriminated between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) from normal human sera (NHS) groups of anti-RalA autoantibody with area under the curve (AUC) of 0.861 (PCa vs NHS) and 0.788 (BPH vs NHS), respectively (Figure 2A)
A statistically significant increase in the frequency of anti-RalA autoantibody was observed across these three study groups (P for trend < 0.001), there was no significant difference between PCa and BPH group
Summary
Prostate cancer (PCa) is the most frequently diagnosed cancer (28%) and the second leading cause of male cancer deaths (10%) in the U.S, with an estimated 220,800 cases and 27,540 deaths in 2015 [1]. The prevention and early detection of PCa, and the identification of patients that are likely to develop aggressive tumors, are issues of major concern in the fight against this malignancy. While the sensitivity www.impactjournals.com/oncotarget of the PSA test is exceptional, its specificity, at lower PSA levels, remains controversial [8,9,10,11]. Because of these limitations and the heterogeneity of PCa and other diseases of the prostate, there is a critical need for additional, more specific biomarkers that could complement PSA in the early detection and management of PCa
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