Tingting Wang1, Hongchun Liu2, Lu Pei3, Kaijuan Wang4, Chunhua Song4, Peng Wang4, Hua Ye4, Jianying Zhang5, Zhenyu Ji6, Songyun Ouyang7, Liping Dai8. 1. Department of Medical Examination in the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Clinical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou 451464, Henan, China. 2. Department of Medical Examination in the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan, China. 3. Department of Medical Examination in the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Clinical Laboratory, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China. 4. Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou 450052, Henan, China. 5. 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. 6. Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. 7. Department of Respiratory and Sleep Medicine in the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: ouyangsy@163.com. 8. Department of Respiratory and Sleep Medicine in the First Affiliated Hospital, 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
OBJECTIVES: The purpose of this study is to discover novel tumor-associated antigens (TAAs) to improve the diagnosis of lung cancer (LC). MATERIALS AND METHODS: Oncomine database was used to discover potential TAAs from LC tissues, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of autoantibodies against TAAs in two independent sets (identification set, n = 368; validation set, n = 1011). RESULTS: Analyses of sera from identification set showed that the sensitivity of autoantibodies against five TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) reached 57.1%, 42.4%, 38.0%, 36.4% and 20.7%, with area under ROC curve (AUC) of 0.85, 0.75, 0.71, 0.73 and 0.70, respectively. It also validated the diagnostic performances of these autoantibodies with AUC of 0.72, 0.65, 0.61, 0.64 and 0.64, respectively. Autoantibody against HMGB3 exhibited significantly increased frequency in early LC (53.3%) compared to advanced LC (29.3%) (P < .05). The positive rates of autoantibody against HMGB3 and NUSAP1 in serum of LC patients without distant metastasis were significantly higher than that of distant metastatic LC (P < .05). When each of the three protein biomarkers (CEA, CA125 and CYFRA21-1) was combined with anti-HMGB3 autoantibody, the sensitivity of early LC increased to 72.7%, 63.3% and 75.9% from 36.4%, 13.3% and 27.6%, respectively. CONCLUSION: Autoantibodies against 5 TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) might have favorable diagnostic values in LC detection, and autoantibody against HMGB3 has the potential to serve as a serological biomarker in early-stage LC. The combination of protein biomarkers and anti-HMGB3 might contribute to detection of early-stage LC.
OBJECTIVES: The purpose of this study is to discover novel tumor-associated antigens (TAAs) to improve the diagnosis of lung cancer (LC). MATERIALS AND METHODS:Oncomine database was used to discover potential TAAs from LC tissues, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of autoantibodies against TAAs in two independent sets (identification set, n = 368; validation set, n = 1011). RESULTS: Analyses of sera from identification set showed that the sensitivity of autoantibodies against five TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) reached 57.1%, 42.4%, 38.0%, 36.4% and 20.7%, with area under ROC curve (AUC) of 0.85, 0.75, 0.71, 0.73 and 0.70, respectively. It also validated the diagnostic performances of these autoantibodies with AUC of 0.72, 0.65, 0.61, 0.64 and 0.64, respectively. Autoantibody against HMGB3 exhibited significantly increased frequency in early LC (53.3%) compared to advanced LC (29.3%) (P < .05). The positive rates of autoantibody against HMGB3 and NUSAP1 in serum of LCpatients without distant metastasis were significantly higher than that of distant metastatic LC (P < .05). When each of the three protein biomarkers (CEA, CA125 and CYFRA21-1) was combined with anti-HMGB3 autoantibody, the sensitivity of early LC increased to 72.7%, 63.3% and 75.9% from 36.4%, 13.3% and 27.6%, respectively. CONCLUSION: Autoantibodies against 5 TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) might have favorable diagnostic values in LC detection, and autoantibody against HMGB3 has the potential to serve as a serological biomarker in early-stage LC. The combination of protein biomarkers and anti-HMGB3 might contribute to detection of early-stage LC.