Proteoglycan 4 is a diagnostic biomarker for COPD

Abstract

Kang-Yun Lee,1,2 Hsiao-Chi Chuang,1,3 Tzu-Tao Chen,1 Wen-Te Liu,1,3 Chien-Ling Su,1,3 Po-Hao Feng,1,2 Ling-Ling Chiang,1,3 Mauo-Ying Bien,3,4 Shu-Chuan Ho3 1Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 2Department of Internal Medicine, School of Medicine, 3School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan Introduction: The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases.Objective: The objective of this study is to discover a diagnostic biomarker for COPD.Methods: Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected. CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects. Receiver operating characteristic values of CRP and the identified biomarkers were determined. A validation COPD cohort was used to reexamine the identified biomarker. Correlation of the biomarker with 1-year lung function decline was determined.Results: Proteoglycan 4 (PRG4) was identified as a biomarker in COPD. The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05). PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency. There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R2=0.91, P=0.013).Conclusion: PRG4 may be a biomarker for identification of severity in COPD. It was related to the 1-year forced vital capacity decline in COPD patients. Keywords: C-reactive protein, exacerbation, inflammation, lung function decline