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Background  Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 ( GPR155 ), a cell surface signaling protein, as a candidate biomarker.    Methods  We analyzed  GPR155  expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of  GPR155  expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection.    Results    GPR155  mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines.  GPR155  mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of  GPR155  mRNA. Downregulation of  GPR155  was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of  GPR155  were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower  GPR155  expression than those with intrahepatic (liver confined) recurrences.    Conclusions  Downregulation of  GPR155  may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.    Electronic supplementary material  The online version of this article (10.1186/s12885-017-3629-2) contains supplementary material, which is available to authorized users.

Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma