Evaluation and characterization of anti-RalA autoantibody as a potential serum biomarker in human prostate cancer.

Evaluation and characterization of anti-RalA autoantibody as a potential serum biomarker in human prostate cancer.
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DOI:
10.18632/oncotarget.9869
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发表时间:
2016-07-12
期刊:
影响因子:
--
通讯作者:
Zhang JY
Zhang JY
中科院分区:
其他
文献类型:
--
作者:
Li J;Dai L;Lei N;Xing M;Li P;Luo C;Casiano CA;Zhang JY

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抗细胞内肿瘤相关抗原(TAA)的自身抗体在人类癌症中很常见。在这项研究中,我们研究了前列腺癌(PCa)患者血清对Rala、Ras样GTP酶的自身抗体反应。用免疫荧光法、酶联免疫吸附试验和免疫印迹法检测了339例前列腺癌和良性前列腺增生症(BPH)患者及正常人血清中的自身抗体。采用免疫组织化学方法(IHC)检测Rala在前列腺癌组织中的表达。英国国民健康保险制度的自身抗体水平(中位数)显著低于前列腺癌(0.053 vs 0.138;P<0.001)和良性前列腺增生症(0.053 vs 0.132;P<0.005)组。循环抗RALA自身抗体可区分PCa患者和正常人,其受试者工作特征曲线下面积为0.861,敏感性为52.9%,特异性为91.0%。前列腺癌根治术后患者血清免疫反应性升高。联合使用抗RALA自身抗体和PSA显示出比单独使用这两个标记物中的任何一个更高的区分能力。免疫组织化学检测85.3%的前列腺癌组织中有Rala蛋白表达,但与良性前列腺增生症及正常对照组织相比无显著差异。总之,我们的研究显示了抗RALA自身抗体作为潜在的PCa血清生物标记物的额外好处,特别是在PSA正常的患者中,并进一步证明了生物标记物组合在PCa免疫诊断中的应用。
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.
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