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
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Liping Dai1,2,3, Yanhong Qu3,5, Jitian Li2, Xiao Wang1, Kaijuan Wang3,4, Peng Wang3,4, Bing-Hua Jiang6 and Jianying Zhang1,2,3
1Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, China
2Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA
3Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, 450052, China
4Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450052, China
5The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450052, China
6Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA
Liping Dai, email: email@example.com
Jianying Zhang, email: firstname.lastname@example.org
Keywords: alpha-enolase (ENO1), non-small cell lung cancer (NSCLC), tumor associated-antigens (TAAs), autoantibody, serological proteome analysis (SERPA)
Received: November 18, 2016 Accepted: March 22, 2017 Published: April 12, 2017
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.
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