Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules

Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice.