Serological proteome analysis approach-based identification of ENO1 as a tumor-associated antigen and its autoantibody could enhance the sensitivity of CEA and CYFRA 21-1 in the detection of non-small cell lung cancer.
Serological proteome analysis approach-based identification of ENO1 as a tumor-associated antigen and its autoantibody could enhance the sensitivity of CEA and CYFRA 21-1 in the detection of non-small cell lung cancer.
复制标题
基于血清学蛋白质组分析方法鉴定ENO1作为肿瘤相关抗原及其自身抗体可增强CEA和CYFRA 21-1检测非小细胞肺癌的敏感性
DOI：
10.18632/oncotarget.17067
复制
发表时间：
2017-05-30
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Dai L;Qu Y;Li J;Wang X;Wang K;Wang P;Jiang BH;Zhang J
目的肺癌(LC)是全球男性和女性癌症相关死亡的主要原因。早期发现LC可使5年生存率提高48.8%，而晚期/远期仅为3.3%。抗肿瘤相关抗原(TAA)的自身抗体已被描述为在肺癌和其他癌症的临床症状之前就存在。我们的目标是找到更多的TAA，以提高从健康个体中发现非小细胞肺癌(NSCLC)患者的性能。方法本研究包括两个独立的样本集。用血清学蛋白质组分析(SERPA)从发现集中的非小细胞肺癌细胞系H1299中鉴定TAA。在验证性研究中，用免疫分析法检测了242例非小细胞肺癌患者和270例正常人血清中抗ENO1自身抗体。结果SERPA鉴定出一个47 KDa的蛋白为α-烯醇化酶(ENO1)。结果表明，非小细胞肺癌患者血清中抗eNO1自身抗体阳性率明显高于正常人，其AUC(95%CI)为0.589(0.539~0.638，P=0.001)。不同分期、不同组织学类型、不同转移状态的NSCLC中，抗ENO1抗体阳性率差异无统计学意义。联合检测ENO1抗体和CEA、Cyfra 21-1标志物，诊断NSCLC的敏感度提高到84%。结论ENO1可诱导非小细胞肺癌的体液免疫应答，其自身抗体与非小细胞肺癌的发生发展有关。此外，这些有趣的结果表明，抗ENO1的自身抗体可能成为非小细胞肺癌潜在的诊断生物标记物，并对确定新的非小细胞肺癌组织学决定因素有意义。
Purpose Lung cancer (LC) is the leading cause of cancer-related deaths for both male and female worldwide. Early detection of LC could improve five-year survival rate up to 48.8% compared to 3.3% of late/distant stage. Autoantibodies to tumor-associated antigens (TAAs) have been described as being present before clinical symptoms in lung and other cancers. We aimed to identify more TAAs to improve the performance for discovering non-small cell lung cancer (NSCLC) patients from healthy individuals. Methods Two independent sets were included in this study. Serological proteome analysis (SERPA) was used to identify TAAs from NSCLC cell line H1299 in a discovery set. In validation study, anti-ENO1 autoantibody was examined by immunoassay in sera from 242 patients with NSCLC and 270 normal individuals. Results A 47 KDa protein was identified to be alpha-enolase (ENO1) by using SERPA. Analysis of sera from 512 participants by ELISA showed significantly higher frequency of anti-ENO1 autoantibodies in NSCLC sera compared with the sera from normal individuals, with AUC (95%CI) of 0.589 (0.539-0.638, P=0.001). There was no significant difference in frequency of anti-ENO1 in different stages, histological or metastasis status of NSCLC. When anti-ENO1 detection was combined with other two tumor protein biomarkers (CEA and CYFRA 21-1), the sensitivity of NSCLC increased to 84%. Conclusions ENO1 can elicit humoral immune response in NSCLC and its autoantibody has association with the tumorigenesis of NSCLC. Furthermore, these intriguing results suggest the possibility of autoantibody against ENO1 serving as a potential diagnostic biomarker in NSCLC and have implications for defining novel histological determinants of NSCLC.