Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer
Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer
复制标题
DOI：
10.1073/pnas.97.8.4198
复制
发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Chen, YT
中科院分区：
文献类型：
--
作者：
Güre, AO;Stockert, E;Chen, YT
用小细胞肺癌患者混合血清对两个小细胞肺癌细胞系的表达文库进行血清学分析，共分离到14个基因，包括4个SOX B组基因(SOX1、SOX2、SOX3和SOX21)和ZIC2。SOX B组基因和ZIC2编码DNA结合蛋白：SOX B组蛋白在辅因子存在的情况下调节靶基因的转录，而ZIC2也被认为是转录调节因子。这些基因在胚胎神经系统的早期发育阶段表达，但在成人中表达下调。虽然在一些成体组织中也能检测到SOX2的mRNA。ZIC2只在脑和睾丸中表达，而SOX1、SOX3和SOX21转录本在正常成人组织中检测不到。在所检测的SCLC细胞系中，80%的细胞表达ZIC2mRNA，SOX1、SOX2和SOX3的表达分别为40%、50%和10%。SOX B组和ZIC2抗原可在30-40%的小细胞肺癌患者中引起血清学反应，滴度可达1：10(6)。在23例正常成人血清中，除1例低滴度抗SOX2抗体外，其余均未检测到抗SOXB或ZIC2蛋白抗体。SOX1和SOX2的抗体效价始终高于SOX3和21，提示SOX1和/或SOX2是引起抗SOX反应的主要抗原。虽然副肿瘤神经系统综合征与几种SCLC抗原有关，但在抗SOX或抗ZIC2抗体阳性的患者中尚未观察到神经系统症状。
Serological analysis of expression cDNA libraries (SEREX) derived from two small cell lung cancer (SCLC) cell lines using pooled sera of SCLC patients led to the isolation of 14 genes, including 4 SOX group B genes (SOX1, SOX2, SOX3, and SOX21) and ZIC2. SOX group B genes and ZIC2 encode DNA-binding proteins: SOX group B proteins regulate transcription of target genes in the presence of cofactors, whereas ZIC2 is also suspected to be a transcriptional regulator. These genes are expressed at early developmental stages in the embryonic nervous system, but are down-regulated in the adult. Although SOX2 mRNA can be detected in some adult tissues. ZIC2 is expressed only in brain and testis, and SOX1, SOX3, and SOX21 transcripts are not detectable in normal adult tissues. Of SCLC cell lines tested, 80% expressed ZIC2 mRNA, and SOX1, SOX2, and SOX3 expression was detected in 40%, 50%, and 10%, respectively. SOX group B and ZIC2 antigens elicited serological responses in 30-40% of SCLC patients in this series, at titers up to 1:10(6). In sera from 23 normal adults, no antibody was detected against SOX group B or ZIC2 proteins except for one individual with low-titer anti-SOX2 antibody. Seroreactivity against SOX1 and 2 was consistently higher titered than SOX3 and 21 reactivity, suggesting SOX1 and/or SOX2 as the main antigens eliciting anti-SOX responses. Although paraneoplastic neurological syndromes have been associated with several SCLC antigens, neurological symptoms have not been observed in patients with anti-SOX or anti-ZIC2 antibodies.