The Prognostic Impact of Leucine-Rich a-2-Glycoprotein-1 in Cholangiocarcinoma and Its Association With the IL-6/TGF- b 1 Axis

Background: Leucine-rich α-2-glycoprotein-1 (LRG) has been found to participate in the development of various cancers through its involvement in TGF-β1-induced epithelial-mesenchymal transition (EMT) and/or angiogenesis and can be induced by inflammatory cytokines, such as IL-6. As we previously showed the implication of IL-6/TGF-β axis in EMT of cholangiocarcinoma cells, we herein explored the prognostic impact of LRG in postoperative intrahepatic cholangiocarcinoma (ICC) and assessed the association between tumor LRG and factors such as TGF-β1, IL-6, and the tumor microvessel density. Methods: We determined the expression of LRG, IL-6, TGF-β1, and CD31 in cancer tissues from 50 ICC patients by immunohistochemistry and analyzed their association with the prognosis. Results: The LRG expression was closely associated with recurrence-free survival (RFS) and overall survival (OS) in postoperative ICC. A multivariate Cox regression model indicated that LRG as an independently associated with poor RFS (hazard ratio = 2.4339, P = 0.0354) and OS (hazard ratio = 2.8892, P = 0.0268). The LRG expression was significantly associated with the expression of TGF-β1 (P = 0.0003) and IL-6 (P = 0.0164). Conclusions: The upregulation of LRG in tumors was an independent prognostic factor in patients with postoperative ICC. LRG was closely associated with the TGF-β1 expression and seems to be an important member of the IL-6/TGF-β1 axis. © 2020 Elsevier Inc.