TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia

Abstract

ObjectiveBiliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.MethodsA total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.ResultsLECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; rs = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.ConclusionLECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.

Progress in Biomarkers Related to Biliary Atresia

“…Another study found that LECT2 was also highly expressed in the sera of children with BA. 102 Dong et al . 103 used miRNA microarray analysis to screen differentially expressed microRNAs (miRNAs) in the sera of patients with BA and those with non-BA neonatal cholestasis.…”

“…Another study found that LECT2 was also highly expressed in the sera of children with BA. 102 Dong et al 103 used miRNA microarray analysis to screen differentially expressed micro-RNAs (miRNAs) in the sera of patients with BA and those with non-BA neonatal cholestasis. They found that the expression levels of miR-4429 were significantly downregulated whereas those of miR-4689 were significantly upregulated in the sera of patients with BA, suggesting that miR-4429 and miR-4689 could serve as potential diagnostic biomarkers of BA.…”

“…An increasing number of serum biomarkers with diagnostic and prognostic value in BA have been discovered and promoted in recent years. Most of them are listed in Table 3, 16,[31][32][33][34][35][36][37]40,42,52,54,59,69,70,72,[75][76][77]83,87,[92][93][94][95][96][97][98][99][100][102][103][104][105][106][107][108][110][111][112][113] including all the biomarkers mentioned in this review. Among them, MMP-7 is currently the most reliable biomarker for the diagnosis of BA, which may help clinicians assess the stage of liver fibrosis and predict post-KPE outcomes to a certain extent.…”

Global research trends and hotspots for leukocyte cell-derived chemotaxin-2 from the past to 2023: a combined bibliometric review

“…The diagnosis of diseases is also a hot research direction of LECT2, especially for tumors like HCC and breast cancer (13,40,47,48). BA is the fifth research hotspot to study the mechanism of LECT2-induced liver fibrosis in patients with Biliary Atresia (49). We drew a mechanism diagram by Figdraw to illustrate how LECT2 affects the development of related diseases, including HCC, liver fibrogenesis, bacterial sepsis, inflammatory response (Figure 9).…”

Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease

“…It has been shown that LECT2 levels were 31.2 (20.9, 41.5) ng/mL in the group of people with NAFLD compared to those without NAFLD, which was significantly higher than in the group without NAFLD ( 37 ). It is proposed that LECT2 is highly expressed in both hepatic tissue and serum in biliary atresia (BA), suggesting that LECT2 can be used as a biomarker for BA ( 38 ). LECT2 levels are increased in patients with metabolic syndrome (MetS) and correlate with severity, suggesting that LECT2 can be used as a biomarker for MetS ( 39 ).…”