Department of Laboratory Medicine Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamiharaminami-ku, Kanagawa 252-0374, Japan.
Int J Oncol. 2011 Dec;39(6):1553-8. doi: 10.3892/ijo.2011.1185. Epub 2011 Sep 5.
C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG) and ceruloplasmin (CP) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In contrast, α2-macroglobulin (α2M) is involved in inflammation through its function as a carrier protein of IL-6. We had previously reported on advanced prostate cancer (PCa) patients with multiple distant bone metastases in whom serum α2M levels were markedly decreased (α2M deficiency). However, the relationship between serum levels of α2M and acute inflammatory biomarkers in PCa patients with or without α2M deficiency has not been demonstrated. In the present study, we examined serum levels of CRP, SAA, IL-6, α1AT, α1AG and CP in PCa patients with or without α2M deficiency to establish clinical significance and changes in these biomarkers during PCa disease progression. We found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients with α2M deficiency, since a function of α2M is to bind and stabilize IL-6, the α2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum levels of the α2M-independent markers, α1AT, α1AG and CP, in all PCa patients regardless of α2M deficiency were significantly higher than in healthy controls, but those of the α2M-dependent molecules, CRP, SAA and IL-6, were not increased in PCa patients with α2M deficiency. Therefore, quantitation of both α2M-dependent (CRP, SAA and IL-6) and α2M-independent (α1AT, α1AG and CP) acute inflammatory biomarkers in advanced PCa patients may be an auxiliary indicator, together with prostate-specific antigen (PSA), to monitor PCa disease progression.
C 反应蛋白（CRP）、血清淀粉样蛋白 A（SAA）、白细胞介素 6（IL-6）、α1-抗胰蛋白酶（α1AT）、α1-酸性糖蛋白（α1AG）和铜蓝蛋白（CP）是急性炎症生物标志物，在感染、炎症、恶性肿瘤和组织损伤等多种情况下都会增加。相比之下，α2-巨球蛋白（α2M）通过作为 IL-6 的载体蛋白参与炎症。我们之前曾报道过患有多处远处骨转移的晚期前列腺癌（PCa）患者，他们的血清 α2M 水平显著降低（α2M 缺乏）。然而，PCa 患者中有无 α2M 缺乏时，血清 α2M 水平与急性炎症生物标志物之间的关系尚未得到证实。在本研究中，我们检测了伴有或不伴有 α2M 缺乏的 PCa 患者的血清 CRP、SAA、IL-6、α1AT、α1AG 和 CP 水平，以确定这些生物标志物在 PCa 疾病进展过程中的临床意义和变化。我们发现，在向伴有 α2M 缺乏的 PCa 患者的血清中添加重组白细胞介素 6（rIL-6）后，由于 α2M 的功能是结合并稳定 IL-6，因此无法检测到 α2M-IL-6 复合物和内源性游离 IL-6。所有 PCa 患者（无论是否存在 α2M 缺乏）的 α2M 非依赖性标志物α1AT、α1AG 和 CP 的血清水平均明显高于健康对照组，但在伴有 α2M 缺乏的 PCa 患者中，α2M 依赖性分子 CRP、SAA 和 IL-6 的水平并未升高。因此，定量检测晚期 PCa 患者的 α2M 依赖性（CRP、SAA 和 IL-6）和 α2M 非依赖性（α1AT、α1AG 和 CP）急性炎症生物标志物，可能与前列腺特异性抗原（PSA）一起成为监测 PCa 疾病进展的辅助指标。
