ANKRD1 and SPP1 as diagnostic markers and correlated with immune infiltration in biliary atresia

The diagnosis of biliary atresia (BA) remains a clinical challenge, reliable biomarkers that can easily distinguish BA and other forms of intrahepatic cholestasis (IC) are urgently needed.Differentially expressed genes were identified by R software. The least absolute shrinkage and selection operator regression and support vector machine algorithms were used to filter the diagnostic biomarkers of BA. The candidate biomarkers were further validated in another independent cohort of patients with BA and IC. Then CIBERSORT was used for estimating the fractions of immune cell types in BA. Gene set enrichment analyses were conducted and the correlation between diagnostic genes and immune cells was analyzed.A total of 419 differentially expressed genes in BA were detected and 2 genes (secreted phosphoprotein 1 [SPP1] and ankyrin repeat domain [ANKRD1]) among them were selected as diagnostic biomarkers. The SPP1 yielded an area under the curve (AUC) value of 0.798 (95% confidence interval [CI]: 0.742-0.854) to distinguish patients with BA from those with IC, and ANKRD1 exhibited AUC values of 0.686 (95% CI: 0.616-0.754) in discriminating BA patients and those with IC. Further integrating them into one variable resulted in a higher AUC of 0.830 (95% CI: 0.777-0.879). The regulatory T cells, M2 macrophages cells, CD4 memory T cells, and dendritic cells may be involved in the BA process. The ANKRD1 and SPP1 was negatively correlated with regulatory T cells.In conclusion, the ANKRD1 and SPP1 could potentially provide extra guidance in discriminating BA and IC. The immune cell infiltration of BA gives us new insight to explore its pathogenesis.