Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudthaya Road, Rajathevi, Bangkok, 10400, Thailand.
Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Sci Rep. 2021 Aug 17;11(1):16695. doi: 10.1038/s41598-021-95805-x.
This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.
本研究旨在确定软骨寡聚基质蛋白（COMP）的 mRNA 和蛋白水平是否与胆道闭锁（BA）患者的临床参数相关，COMP 是一种负责调节细胞外基质动态平衡的糖蛋白，其在全身和局部肝脏环境中的表达。采用酶联免疫吸附试验、实时聚合酶链反应和免疫组织化学法分别检测了 96 例 BA 患者和 56 例健康对照者循环中的 COMP 蛋白水平及其在 20 例 BA 患者和 5 例非 BA 患者肝脏中的 mRNA 和蛋白表达。BA 患者的循环 COMP 水平明显高于健康对照组。与早期 BA 患者相比，晚期 BA 患者（包括黄疸、纤维化和肝功能障碍）的循环 COMP 水平显著升高。升高的循环 COMP 水平与肝纤维化程度呈独立相关。生存分析表明，循环 COMP 水平升高与 BA 患者的生存率降低显著相关。受试者工作特征曲线分析揭示了循环 COMP 作为 BA 非侵入性生物标志物的诊断价值（AUC=0.99），其灵敏度为 100.0%，特异性为 98.2%。在肝脏中，纤维化的 BA 患者的 COMP mRNA 和蛋白表达均明显高于无纤维化的 BA 患者和非 BA 患者。总之，循环 COMP 的增加可能反映了 BA 患者的不良预后，并且可能成为 Kasai 手术后疾病严重程度的新型生物标志物。
