• Wenhao Su, Tong Qiu, Meng Zhang, Cui Hao, Pengjiao Zeng, Zhangfeng Huang, Wenxing Du, Tianxiang Yun, Yunpeng Xuan, Lijuan Zhang, Yachong Guo, and Wenjie Jiao.
• Systems Biology & Medicine Center for Complex Diseases, Center for Clinical Research, Affiliated Hospital of Qingdao University, Qingdao, China.
• Curr Med Res Opin. 2022 Feb 1; 38 (2): 201209201-209.

BackgroundMost human diseases are accompanied by systems changes. Systems biomarkers should reflect such changes. The phosphorylation and dephosphorylation of biomolecules maintain human homeostasis. However, the systems biomarker characteristics of circulating alkaline phosphatase, a routine blood test conducted for many human diseases, have never been investigated.MethodThis study retrieved the circulating alkaline phosphatase (ALP) activities from patients with 48 clinically confirmed diseases and healthy individuals from the database of our hospital during the past five years. A detailed analysis of the statistical characteristics of ALP was conducted, including quantiles, receiving operator curve (ROC), and principal component analysis.ResultsAmong the 48 diseases, 45 had increased, and three had decreased median levels of ALP activities compared to the healthy control. Preeclampsia, hepatic encephalopathy, pancreatic cancer, and liver cancer had the highest median values, whereas nephrotic syndrome, lupus erythematosus, and nephritis had decreased median values compared to the healthy control. Further, area under curve (AUC) values were ranged between 0.61 and 0.87 for 19 diseases, and the ALP activities were the best systems biomarker for preeclampsia (AUC 0.87), hepatic encephalopathy (AUC 0.87), liver cancer (AUC 0.81), and pancreatic cancer (AUC 0.81).ConclusionsAlkaline phosphatase was a decent systems biomarker for 19 different types of human diseases. Understanding the molecular mechanisms of over-up-and-down-regulation of ALP activities might be the key to understanding the whole-body systems' reactions during specific disease progression.

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