A preliminary study of ECT2 as a novel biomarker for assessing liver fibrosis and prognosis in biliary atresia.

Background & aims: Biliary atresia (BA) is the leading cause of cholestatic liver disease and cirrhosis in infancy. Currently, there is a lack of efficient biomarkers for early diagnosis and prognostic evaluation of this disease, which urgently needs to be addressed. This study aimed to screen and validate key biomarkers closely associated with BA liver fibrosis progression and prognosis through bioinformatics analysis combined with clinical sample verification. Methods: First, the public transcriptomic dataset GSE122340 was thoroughly analyzed to screen differentially expressed genes, followed by construction of a protein-protein interaction (PPI) network. Epithelial cell transforming sequence 2 (ECT2) was ultimately identified as the core hub gene. Subsequently, clinical samples were collected, including 20 cases in the BA group (stratified by liver fibrosis severity) and 10 cases in the choledochal cyst control group. The expression level of ECT2 was clinically verified using immunohistochemistry, real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was performed to validate the predictive efficacy of serum ECT2 level for BA diagnosis, fibrosis stratification, and postoperative native liver survival. Kaplan-Meier (KM) curve analysis was used to verify the relationship between serum ECT2 level and postoperative native liver survival. Results: ECT2 was significantly highly expressed in liver tissue (both mRNA and protein levels) and serum of BA patients, and its expression intensity was positively correlated with the severity of liver fibrosis. ROC curve analysis showed that serum ECT2 exhibited favorable efficacy in BA diagnosis, liver fibrosis stratification, and prediction of 2-year postoperative native liver survival, with area under the curve (AUC) values of 0.906, 0.807, and 0.844.Compared with MMP7, it demonstrates comparable predictive performance in the diagnosis of BA (AUC = 0.924) and the stratification of liver fibrosis (AUC = 0.829), and outperforms MMP7 in predicting autologous liver survival (AUC = 0.767). Its overall predictive performance is superior to that of traditional liver function markers (GGT, TBIL, TBA). Kaplan-Meier survival analysis further confirmed that BA patients with high serum ECT2 expression had significantly reduced native liver survival rates postoperatively. Conclusion: This study systematically demonstrates that ECT2 is characteristically highly expressed in BA and its association with disease fibrosis severity and poor prognosis. Preliminary findings suggest that serum ECT2 as a promising non-invasive biomarker, providing new technical approaches and theoretical basis for clinical diagnosis, disease assessment, and prognostic judgment of BA.