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Discovery of Potential Serum Protein Biomarkers in Ankylosing Spondylitis Using TMT-Based Quantitative Proteomics

23 Pages Posted: 27 Jul 2019

See all articles by Shijia Liu

Shijia Liu

Nanjing University of Chinese Medicine (NJUCM)

Wei Ji

Nanjing University of Chinese Medicine (NJUCM)

Jiawei Lu

China Pharmaceutical University - State Key Laboratory of Natural Medicines

Xiaojun Tang

Nanjing University - Drum Tower Hospital

Yunke Guo

Nanjing University of Chinese Medicine (NJUCM)

Mingde Ji

Nanjing University of Chinese Medicine (NJUCM)

Tian Xu

Nanjing University of Chinese Medicine (NJUCM)

Wanjian Gu

Nanjing University of Chinese Medicine (NJUCM) - Affiliated Hospital

Deshun Kong

Nanjing University of Chinese Medicine (NJUCM)

Qiuxiang Shen

Nanjing University of Chinese Medicine (NJUCM)

Dandan Wang

Nanjing University

Xiangyu Lv

China Pharmaceutical University - School of Traditional Chinese Pharmacy

Jue Wang

China Pharmaceutical University - School of Traditional Chinese Pharmacy

Tianyao Zhu

Nanjing University of Chinese Medicine (NJUCM)

Youjuan Zhu

Nanjing University of Chinese Medicine (NJUCM)

Ping Liu

Xuzhou Medical University

Jinfeng Su

Xuzhou Medical University

Lu Wang

Xuzhou Medical University

Yuhua Li

Xuzhou Medical University

Pan Gao

Xuzhou Medical University

Wei Liu

Xuzhou Medical University

Lingyun Sun

Nanjing University - Departments of Radiology and Rheumatology

Xiaojian Yin

China Pharmaceutical University - State Key Laboratory of Natural Medicines

Wei Zhou

China Pharmaceutical University - State Key Laboratory of Natural Medicines

More...

Abstract

Background: Ankylosing Spondylitis (AS) is a systemic, chronic and inflammatory rheumatic disease, which affected 0.2% of the population. Current diagnostic criteria relys on a composite of clinical and rediological changes, with an average of 14 years from AS symptoms onset to diagnosis. Here, we aimed to discover a panel of potential biomarkers for AS diagnosis.

Methods: A cohort of 403 patients including 153 AS and 250 healthy subjects from 2 independent centers was studied. In the discovery set 1, TMT-based quantitative proteomics method was applied to identify serum proteins. In the discovery set 2, ELISA method was further performed to quantify and validate the levels of differential proteins from proteomics. An array of potential biomarkers were screened by the area under the receiver operating characteristic (ROC) curve. Finally, an accurate and reliable biomarkers panel was evaluated by the prediction accuracies in internal and external validation sets.

Findings: A total of 762 proteins were identified from 15 pooled AS and 60 pooled healthy serum samples. Among them, 46 up-regulated and 59 down-regulated proteins were identified in AS compared to healthy subjects. The AS responsive proteins including CRP, SAA1, ORM2, FG-γ and THBS1 were validated successfully by ELISA using sera of 36 AS and 36 healthy subjects. The area under the ROC curve of the CRP and SAA1 combination was high, near by 0.9. The sensitivity was 0.970, specificity was 0.805 at 95% confidence interval from 0.811 to 0.977. The predictive values reached 92.00% in the internal validation set (62 AS vs 114 healthy subjects) and 97.50% in the external validation phase (40 AS vs 40 healthy subjects).

Interpretation: A panel of two acute phase proteins (CRP and SAA1) as potential biomarkers could be useful for complementary diagnosis of AS.

Funding: This work is financially supported by the National Natural Science Foundation of China,
the Natural Science Foundation of Jiangsu province, Jiangsu Provincial Medical Youth Talent (No.
QNRC2016642), the Young Elite Scientists Sponsorship Program by CAST (No. QNRC2-B04), Science and technology projects of Jiangsu Province Hospital of TCM (No. Y18010) and the top
six talent project of Jiangsu province 2016 (WSN-051).

Declaration of Interest: There is no any conflict of interest with regard to our work.

Ethical Approval: All procedures were approved by the medical ethics committee of the affiliated Hospital of Nanjing University of Chinese Medicine and followed the tenets of the Declaration of Helsinki. The experimental protocol was reviewed and approved by the Institutional Review Board of the affiliated Hospital of Nanjing University of Chinese Medicine (2018NL-106-02).

Keywords: Biomarker, Ankylosing Spondylitis, CRP, SAA1, Serum proteomics

Suggested Citation

Liu, Shijia and Ji, Wei and Lu, Jiawei and Tang, Xiaojun and Guo, Yunke and Ji, Mingde and Xu, Tian and Gu, Wanjian and Kong, Deshun and Shen, Qiuxiang and Wang, Dandan and Lv, Xiangyu and Wang, Jue and Zhu, Tianyao and Zhu, Youjuan and Liu, Ping and Su, Jinfeng and Wang, Lu and Li, Yuhua and Gao, Pan and Liu, Wei and Sun, Lingyun and Yin, Xiaojian and Zhou, Wei, Discovery of Potential Serum Protein Biomarkers in Ankylosing Spondylitis Using TMT-Based Quantitative Proteomics (July 24, 2019). Available at SSRN: https://ssrn.com/abstract=3426065 or http://dx.doi.org/10.2139/ssrn.3426065

Shijia Liu

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Wei Ji

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Jiawei Lu

China Pharmaceutical University - State Key Laboratory of Natural Medicines

24 Tongjiaxiang
Nanjing
China

Xiaojun Tang

Nanjing University - Drum Tower Hospital

321 Zhong Shan Road
Nanjing, Jiangning District 210008
China

Yunke Guo

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Mingde Ji

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Tian Xu

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Wanjian Gu

Nanjing University of Chinese Medicine (NJUCM) - Affiliated Hospital

Nanjing
China

Deshun Kong

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Qiuxiang Shen

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Dandan Wang

Nanjing University

Nanjing, Jiangsu 210093
China

Xiangyu Lv

China Pharmaceutical University - School of Traditional Chinese Pharmacy

Nanjing
China

Jue Wang

China Pharmaceutical University - School of Traditional Chinese Pharmacy

Nanjing
China

Tianyao Zhu

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Youjuan Zhu

Nanjing University of Chinese Medicine (NJUCM)

Nanjing, 210023
China

Ping Liu

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Jinfeng Su

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Lu Wang

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Yuhua Li

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Pan Gao

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Wei Liu

Xuzhou Medical University

Yunlong
Xuzhou, Jiangsu 221100
China

Lingyun Sun

Nanjing University - Departments of Radiology and Rheumatology ( email )

No. 321 Zhongshan Road,
Nanjing, 210008
China

Xiaojian Yin

China Pharmaceutical University - State Key Laboratory of Natural Medicines ( email )

24 Tongjiaxiang
Nanjing
China

Wei Zhou (Contact Author)

China Pharmaceutical University - State Key Laboratory of Natural Medicines ( email )

24 Tongjiaxiang
Nanjing
China

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