Haptoglobin-β chain defined by monoclonal antibody RM2 as a novel serum marker for prostate cancer
Haptoglobin-β chain defined by monoclonal antibody RM2 as a novel serum marker for prostate cancer
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DOI：
10.1002/ijc.23490
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发表时间：
2008-08-01
影响因子：
6.4
通讯作者：
Arai, Yoichi
中科院分区：
文献类型：
--
作者：
Saito, Seiichi;Murayama, Yasuko;Arai, Yoichi
在我们之前的研究中，针对糖基表位建立的单克隆抗体RM 2反映了前列腺癌细胞的恶性程度，而RM 2对良性腺体的反应性为阴性或较弱。在基质中也检测到RM 2反应性，表明RM 2识别的糖蛋白可以释放到血流中。然后，我们探讨了RM 2对早期前列腺癌血清的反应性。我们比较了62例早期前列腺癌患者和43例良性前列腺疾病患者的血清RM 2反应性，并通过Western印迹法检测了15例患者根治性前列腺切除术前后的RM 2反应性。我们还检查了RM 2对其他泌尿生殖系统癌症血清的反应性。与良性前列腺疾病患者相比，在早期前列腺癌患者中，RM 2对分子量接近40 kDa的血清糖蛋白（此处称为GPX）的反应性显著增强（p < 0.0001）。设定适当的临界值，RM 2对GPX的反应性检测前列腺癌的敏感性和特异性分别为87%和84%。此外，根治性膀胱切除术后RM 2反应性水平显著降低（p = 0.006）。然而，在其他泌尿生殖系统癌症中也观察到RM 2对GPX的反应性增加。蛋白质组学方法鉴定GPX为触珠蛋白-β链，并且当与多克隆抗触珠蛋白抗体相比时，RM 2显示出对来自前列腺癌的触珠蛋白-β链的优先反应性。由RM 2定义的结合珠蛋白-β链是一种新的血清标志物，当与前列腺特异性抗原偶联时，可能用于检测早期前列腺癌，因为它对前列腺癌没有特异性。(C)2008威利利斯公司
In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass similar to 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer. (C) 2008 Wiley-Liss, Inc.