Su Wenhao, Qiu Tong, Zhang Meng, Hao Cui, Zeng Pengjiao, Huang Zhangfeng, Du Wenxing, Yun Tianxiang, Xuan Yunpeng, Zhang Lijuan, Guo Yachong, Jiao Wenjie
Systems Biology & Medicine Center for Complex Diseases, Center for Clinical Research, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Curr Med Res Opin. 2022 Feb;38(2):201-209. doi: 10.1080/03007995.2021.2000715. Epub 2021 Nov 12.
Most 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.
This 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.
Among 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).
Alkaline 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.
大多数人类疾病都伴有系统变化。系统生物标志物应能反映此类变化。生物分子的磷酸化和去磷酸化维持着人体的稳态。然而，对于许多人类疾病常规进行的血液检测项目——循环碱性磷酸酶的系统生物标志物特征，从未进行过研究。
本研究从我院过去五年的数据库中检索了48种临床确诊疾病患者及健康个体的循环碱性磷酸酶（ALP）活性。对ALP的统计特征进行了详细分析，包括分位数、受试者工作特征曲线（ROC）和主成分分析。
在这48种疾病中，与健康对照相比，45种疾病的ALP活性中位数升高，3种疾病的ALP活性中位数降低。子痫前期、肝性脑病、胰腺癌和肝癌的中位数最高，而与健康对照相比，肾病综合征、红斑狼疮和肾炎的中位数降低。此外，19种疾病的曲线下面积（AUC）值在0.61至0.87之间，ALP活性是子痫前期（AUC 0.87）、肝性脑病（AUC 0.87）、肝癌（AUC 0.81）和胰腺癌（AUC 0.81）的最佳系统生物标志物。
碱性磷酸酶是1九种不同类型人类疾病的良好系统生物标志物。了解ALP活性上调和下调的分子机制可能是理解特定疾病进展过程中全身系统反应的关键。
