Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA.
Int J Oncol. 2012 Sep;41(3):1061-7. doi: 10.3892/ijo.2012.1515. Epub 2012 Jun 12.
Hepatocellular carcinoma (HCC) is a type of cancer with a very poor prognosis. Although α-fetoprotein (AFP) is the most effective marker available to detect HCC, the sensitivity and specificity are not optimal. Therefore, there is a need for the development of more sensitive and specific methods that can supplement AFP in the early detection of this cancer. In this study, autoantibody responses to glucose-regulated protein 78 (GRP78) were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting and indirect immunofluorescence assay in sera from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH), as well as from normal human individuals. Immunohistochemistry (IHC) with tissue array slides was also preformed to analyze protein expression profiles of GRP78 in HCC and control tissues. The prevalence of autoantibodies against GRP78 was 35.5% (27/76) in HCC, which was significantly higher than that in LC, CH and normal human sera (NHS; P<0.01). The average titer of autoantibodies against GRP78 in HCC sera was higher compared to that in LC, CH and NHS(P<0.01). When both autoantibodies against GRP78 and AFP were used simultaneously as diagnostic markers, sensitivity reached 71.4%. Our data indicate that anti-GRP78 autoantibodies may be potential diagnostic markers for HCC, especially in conjunction with AFP.
肝细胞癌（HCC）是一种预后非常差的癌症。虽然甲胎蛋白（AFP）是检测 HCC 最有效的标志物，但它的灵敏度和特异性并不理想。因此，需要开发更敏感和特异的方法来补充 AFP 在这种癌症的早期检测中。在这项研究中，通过酶联免疫吸附试验（ELISA）、Western blot 和间接免疫荧光试验评估了自身抗体对葡萄糖调节蛋白 78（GRP78）的反应，在 HCC、肝硬化（LC）和慢性肝炎（CH）患者以及正常人类个体的血清中进行了评估。还使用组织阵列幻灯片进行了免疫组织化学（IHC），以分析 HCC 和对照组织中 GRP78 的蛋白表达谱。在 HCC 患者中，针对 GRP78 的自身抗体的患病率为 35.5%（27/76），明显高于 LC、CH 和正常人类血清（NHS；P<0.01）。与 LC、CH 和 NHS 相比，HCC 血清中针对 GRP78 的自身抗体的平均滴度更高（P<0.01）。当同时将针对 GRP78 和 AFP 的自身抗体用作诊断标志物时，灵敏度达到 71.4%。我们的数据表明，针对 GRP78 的自身抗体可能是 HCC 的潜在诊断标志物，特别是与 AFP 联合使用时。
