Giraudi P J, Pascut D, Banfi C, Ghilardi S, Tiribelli C, Bondesan A, Caroli D, Minocci A, Sartorio A
Metabolic Liver Disease Unit, Fondazione Italiana Fegato-ONLUS, Trieste, Italy.
Liver Cancer Unit, Fondazione Italiana Fegato-ONLUS, Trieste, Italy.
J Endocrinol Invest. 2025 Jan;48(1):213-225. doi: 10.1007/s40618-024-02419-x. Epub 2024 Jul 17.
Childhood obesity, a pressing global health issue, significantly increases the risk of metabolic complications, including metabolic dysfunction associated with steatotic liver disease (MASLD). Accurate non-invasive tests for early detection and screening of steatosis are crucial. In this study, we explored the serum proteome, identifying proteins as potential biomarkers for inclusion in non-invasive steatosis diagnosis tests.
Fifty-nine obese adolescents underwent ultrasonography to assess steatosis. Serum samples were collected and analyzed by targeted proteomics with the Proximity Extension Assay technology. Clinical and biochemical parameters were evaluated, and correlations among them, the individuated markers, and steatosis were performed. Receiver operating characteristic (ROC) curves were used to determine the steatosis diagnostic performance of the identified candidates, the fatty liver index (FLI), and their combination in a logistic regression model.
Significant differences were observed between subjects with and without steatosis in various clinical and biochemical parameters. Gender-related differences in the serum proteome were also noted. Five circulating proteins, including Cathepsin O (CTSO), Cadherin 2 (CDH2), and Prolyl endopeptidase (FAP), were identified as biomarkers for steatosis. CDH2, CTSO, Leukocyte Immunoglobulin Like Receptor A5 (LILRA5), BMI, waist circumference, HOMA-IR, and FLI, among others, significantly correlated with the steatosis degree. CDH2, FAP, and LDL combined in a logit model achieved a diagnostic performance with an AUC of 0.91 (95% CI 0.75-0.97, 100% sensitivity, 84% specificity).
CDH2 and FAP combined with other clinical parameters, represent useful tools for accurate diagnosis of fatty liver, emphasizing the importance of integrating novel markers into diagnostic algorithms for MASLD.
儿童肥胖是一个紧迫的全球健康问题，会显著增加代谢并发症的风险，包括与脂肪性肝病相关的代谢功能障碍（MASLD）。准确的非侵入性检测对于早期发现和筛查脂肪变性至关重要。在本研究中，我们探索了血清蛋白质组，鉴定出可作为非侵入性脂肪变性诊断检测潜在生物标志物的蛋白质。
对59名肥胖青少年进行超声检查以评估脂肪变性。收集血清样本并采用邻位延伸分析技术通过靶向蛋白质组学进行分析。评估临床和生化参数，并分析它们之间、个体化标志物与脂肪变性之间的相关性。使用受试者工作特征（ROC）曲线来确定所鉴定候选物、脂肪肝指数（FLI）及其在逻辑回归模型中的组合对脂肪变性的诊断性能。
在各种临床和生化参数方面，有脂肪变性和无脂肪变性的受试者之间观察到显著差异。还注意到血清蛋白质组存在性别相关差异。鉴定出五种循环蛋白，包括组织蛋白酶O（CTSO）、钙黏蛋白2（CDH2）和脯氨酰内肽酶（FAP）作为脂肪变性的生物标志物。CDH2、CTSO、白细胞免疫球蛋白样受体A5（LILRA5）、体重指数、腰围、稳态模型评估的胰岛素抵抗（HOMA-IR）以及FLI等与脂肪变性程度显著相关。在一个逻辑模型中，CDH2、FAP和低密度脂蛋白（LDL）的组合实现了诊断性能，曲线下面积（AUC）为0.91（95%可信区间0.75 - 0.97，灵敏度100%，特异性84%）。
CDH2和FAP与其他临床参数相结合，是准确诊断脂肪肝的有用工具，强调了将新标志物纳入MASLD诊断算法的重要性。
