Lu Pei1, Hongchun Liu2, Songyun Ouyang3, Chunling Zhao3, Man Liu4, Tingting Wang5, Peng Wang6, Hua Ye6, Kaijuan Wang6, Chunhua Song6, Jianying Zhang4, Liping Dai7. 1. Department of Medical Examination in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Department of Clinical Laboratory, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, China. 2. Department of Medical Examination in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. 3. Department of Respiratory and Sleep Medicine in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. 4. Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, 450052, Henan, China. 5. Department of Clinical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 451464, Henan, China. 6. Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, 450052, Henan, China. 7. Department of Respiratory and Sleep Medicine in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: lpdai@zzu.edu.cn.
Abstract
OBJECTIVE: The identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population. METHODS: In our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set. FINDINGS: Based on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LC patients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively). CONCLUSION: TOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.
OBJECTIVE: The identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population. METHODS: In our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set. FINDINGS: Based on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LCpatients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively). CONCLUSION:TOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.