BACKGROUND: Neuromedin U (NMU) is a neuropeptide belonging to the neuromedin 
family. Recently, significant associations between NMU and several cancers have 
been reported. However, no studies have examined the association between NMU and 
hepatocellular carcinoma (HCC). The purpose of this study was to examine the 
role of NMU in HCC.
METHODS: An enzyme-linked immunosorbent assay was used to measure the level of 
NMU protein in the sera of patients with hepatic hemangioma and HCC. NMU and 
cytokine mRNA expression was assessed in HCC samples via RT-qPCR. A tissue 
microarray consisting of 228 HCC peri- and intra-tumor tissues was used to 
detect NMU expression via immunohistochemical analysis. The association between 
NMU expression and overall survival (OS) and disease-free survival (DFS) was 
analyzed by Kaplan-Meier curves, the log-rank test, and Cox proportional hazard 
model.
RESULTS: The level of NMU protein was increased in the sera of HCC patients 
(p = 0.006). NMU was expressed in intercellular space, rather than in 
hepatocytes or HCC cells. The prognosis of HCC patients with high NMU expression 
in peri-tumor tissue was significantly poorer than that of patients with low NMU 
expression (OS: p = 0.002, DFS: p = 0.033). Peri-tumor NMU expression was also a 
significant independent prognostic factor for OS (hazard ratio: 1.541, 95% 
confidence interval: 1.092-2.175, p = 0.014). The level of NMU expression was 
positively associated with M2 macrophage percentage and the levels of type-2 
inflammatory cytokines in HCC tissue.
CONCLUSIONS: NMU may serve as a novel prognostic biomarker for HCC patients, 
although further validation is needed in the future. The activation of M2 
macrophages and a type-2 inflammatory response may involve in the role of NMU in 
patients with HCC.