Detection and identification of tumor‐associated protein variants in human hepatocellular carcinomas
Detection and identification of tumor‐associated protein variants in human hepatocellular carcinomas
复制标题
DOI：
10.1002/hep.20060
复制
发表时间：
2004-02
期刊：
影响因子：
13.5
通讯作者：
E. Zeindl‐Eberhart;S. Haraida;S. Liebmann;P. Jungblut;S. Lamer;D. Mayer;Gundula Jäger;S. Chung;H. Rabes
中科院分区：
文献类型：
--
作者：
E. Zeindl‐Eberhart;S. Haraida;S. Liebmann;P. Jungblut;S. Lamer;D. Mayer;Gundula Jäger;S. Chung;H. Rabes
蛋白质组学方法是检测和识别与癌症相关的蛋白质的有价值的工具。在以往对实验性大鼠肝癌的研究中，我们检测到醛糖还原酶样蛋白(ARLP)是一种非常重要的标志性蛋白。我们目前的研究旨在寻找在人类肝细胞癌(HCC)中是否存在类似的肿瘤相关标记蛋白。我们发现了几个新的肿瘤相关蛋白变体，代表了醛酮还原酶(AKR)超家族的成员。人醛糖还原酶样蛋白-1(hARLP-1)是双向凝胶电泳法(2-DE)检测到的肝癌组织中最显著的肿瘤相关AKR成员，并经质谱仪指纹图谱鉴定。HARLP-1，36/7.4(kd/pI)；hARLP-2，36/7.2；hARLP-3，36/6.4；hARLP-4，33/7.35。此外，还发现了一个人醛糖还原酶样蛋白(hARLP-5，36/7.6)，与hARLP-1相差1个氨基酸(D313N)，表明该基因有两种等位基因形式。一种新的针对hARLP共同部分的抗体通过免疫组织化学显示hARLP在人肝细胞癌中呈阳性反应。此外，醛糖还原酶(AR)被鉴定为肿瘤相关变异体。总之，在所有被研究的人肝癌中，至少有一种所描述的AKR超家族的肿瘤相关蛋白是明确存在的。经2-DE分析和/或使用针对hARLP的抗体证实，这些肝细胞癌样本中95%为hARLP阳性。因此，hARLP是作为人肝细胞癌免疫组织化学诊断标记物的有力候选者。(《肝病》2004；39：540-549。)
The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase‐like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor‐associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumor‐associated protein variants that represent members of the aldo‐keto reductase (AKR) superfamily. Human aldose reductase‐like protein‐1 (hARLP‐1) was the most prominent tumor‐associated AKR member detected in HCC by 2‐dimensional electrophoresis (2‐DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms (hARLP‐1, 36/7.4 (kd/pI); hARLP‐2, 36/7.2; hARLP‐3, 36/6.4; and hARLP‐4, 33/7.35). In addition, a human aldose reductase‐like protein (hARLP‐5, 36/7.6) was identified that differed from hARLP‐1 by 1 amino acid (D313N), indicating 2 allelic forms of the human aldose reductase‐like gene. A novel antibody directed against common parts of the hARLPs revealed hARLP reactivity in human HCC by immunohistochemistry. Furthermore, aldose reductase (AR) was identified and characterized as a tumor‐associated variant. In conclusion, in all investigated human HCCs at least one of the various types of the described tumor‐associated proteins of the AKR superfamily was clearly present. Of these HCC samples, 95% were positive for hARLPs as proven by 2‐DE analysis and/or by use of the antibody directed against hARLP. Thus, hARLP is a strong candidate for use as an immunohistochemical diagnostic marker of human HCC. (HEPATOLOGY 2004;39:540–549.)