Abstract
PurposeLung 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.MethodsTwo 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.ResultsA 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%.ConclusionsENO1 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.
Highlights
Lung cancer (LC) is the leading cause of cancerrelated deaths for both male and female worldwide
Analysis of sera from 512 participants by Enzyme-linked immunosorbent assay (ELISA) showed significantly higher frequency of anti-ENO1 autoantibodies in non-small cell lung cancer (NSCLC) sera compared with the sera from normal individuals, with area under the curve (AUC) (95%confidence interval (CI)) of 0.589 (0.539-0.638, P=0.001)
When anti-ENO1 detection was combined with other two tumor protein biomarkers (CEA and CYFRA 21-1), the sensitivity of NSCLC increased to 84%
Summary
Lung cancer (LC) is the leading cause of cancerrelated deaths for both male and female worldwide. Until 2007, the five-year overall survival rate for LC patients is only 16% among all cancers [2]. Detection of LC could improve five-year survival rate up to 48.8% compared to 3.3% of late/distant stage [3]. Low dose spiral computed tomography (LDCT) is the limited approach to screen LC in atrisk individuals in early detection of LC [4, 5]. The identification and validation of a cost-effective early stage blood test to complement LDCT screening is essential. Serum biomarker detection, which possesses advantages such as easy operation, low cost, noninvasiveness, accessibility of samples, is a high-profile topic for detection of early LC [9]. We have recently reported that elevated autoantibody levels could be detected in patients’ sera at least four years before the diagnosis of LC [13]
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