WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor
WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor
复制标题
DOI：
10.1002/ijc.24367
复制
发表时间：
2009-07-15
影响因子：
6.4
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
--
作者：
Oji, Yusuke;Kitamura, Yayoi;Sugiyama, Haruo
非小细胞肺癌（nonsmall cell lung cancer，NSCLC）的发病率逐年上升，预后差，迫切需要建立早期检测方法。在这里，我们分析了针对在大多数NSCLC中过表达的WT 1（Wilms肿瘤基因）蛋白的IgG抗体（WT 1 Ab）的产生。酶联免疫吸附试验显示91例NSCLC患者和70例健康人均产生WT 1抗体，且NSCLC患者的WT 1抗体滴度明显高于健康人。当WT 1抗体的临界值固定为健康人的平均值± 3SD时，26.4%的NSCLC患者的WT 1抗体滴度超过临界值，I、II和III期NSCLC中各临床分期的WT 1抗体阳性率分别为25.0%、30.8%和38.4%。当WT 1 Ab与CEA或CYFRA联合检测NSCLC时，I期的阳性检出率分别从25.0%增加到34.1%和31.8%，III期的阳性检出率分别从38.4%增加到69.2%和46.1%，但II期无变化。Western blot分析表明，WT 1抗体的优势亚类为Th 1型IgG 2。有趣的是，WT 1 Ab滴度升高与I-III期NSCLC患者的无病生存期延长显著相关。提示WT 1抗体可作为NSCLC早期诊断及预后判断的一个有用指标。这些结果也表明WT 1特异性免疫应答在NSCLC的抗癌免疫中起重要作用。(C)2009年UICC
There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC. (C) 2009 UICC