Abstract
The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (WGCNA). The biological processes and signal pathways that biomarkers involved in were further analyzed by bioinformatics. Quantitative Real-time PCR, Western blot and immunohistochemistry was performed to detect biomarkers expression. The relationship of biomarkers with clinicopathological characteristics of BA was also investigated. LECT2 was overexpressed or knockdown in LX-2 cells, and the expression of fibrogenic genes such as a-SMA and COL1A1 was quantified. We found that LECT2 mRNA expression was higher in BA liver tissues compared with normal liver tissues. Bioinformatics showed that LECT2 mainly played a fibrosis-promoting role in the development in BA by regulating bile acid metabolism and promoting inflammatory response. LECT2 immunohistochemistry scores of BA children were higher than control group (p = 0.001). Survival analysis revealed that LECT2 high expression is an unfavorable prognostic factor for native liver survival in BA patients. Additionally, the high LECT2 expression was an independent prognostic factor affecting native liver survival (HR 3.702, 95%CI:2.085–6.575, p = 0.001). LECT2 modulates TGF-β mediated a-SMA and COL1A1 expression in LX-2 cells. siRNA-LECT2 inhibits the expression of a-SMA and COL1A1 in LX-2 cells. Overexpression of LECT2 resulted in an increase in a-SMA and COL1A1 expression. Knockdown of LECT2 inhibits the proliferation and increase apoptosis in activated LX-2 cells. LECT2 may act as a new prognostic biomarker for native liver survival in BA patients.
Highlights
Biliary atresia (BA) is a severe, progressive obstructive biliary disease that occurs in infancy and is a common cause of neonatal jaundice (Hartley et al, 2009)
Biliary atresia is a common cause of pathological jaundice in infants, with complex etiology, and the major pathological changes of biliary atresia (BA) were collagen deposition and liver tissue fibrosis, which can eventually lead to death of the child (Cielecka-Kuszyk et al, 2021)
Studies have shown that liver fibrosis plays an important role in the course of BA and that the process of liver fibrosis does not stop after Kasai surgery in children with BA (Zhou et al, 2016)
Summary
Biliary atresia (BA) is a severe, progressive obstructive biliary disease that occurs in infancy and is a common cause of neonatal jaundice (Hartley et al, 2009). Inflammatory bile duct obstruction and liver fibrosis are the key factors affecting the survival of children with BA. Since the Kasai procedure was performed in 1959, the prognosis of BA children has gradually improved (Chardot et al, 1999). Despite the Kasai procedure, more than 60% of children still need liver transplantation to save their lives due to recurrent cholangitis and cholestatic cirrhosis after surgery (He et al, 2021). Kasai surgery does not stop the progression of liver fibrosis, and about 70–80% of children with liver fibrosis continue to progress, affecting long-term prognosis (Bijl et al, 2013). How to prolong the survival time of native liver in BA children and delay liver transplantation is an urgent clinical problem
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