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

Abstract

BackgroundMolecular 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.MethodsWe 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.ConclusionsDownregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3629-2) contains supplementary material, which is available to authorized users.

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

“…This phenotype was similar to what appeared in bone morphogenetic protein (BMP) signaling gain-of-function experiments [78]. GPR155 has also been linked to a number of different cancers [79,80].…”

Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer

“…The key gene GPR155 in the blue module has also been extensively studied in cancers. In addition to its role as a biomarker in GC, the downregulation of GPR155 was reported as significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage (Umeda et al, 2017). The presence of GPR155 in multiple gene pairs suggest it might be a crucial regulatory gene in GC and this offers clues for carrying out its further research in cancers.…”

Genetic Characteristics Associated With Drug Resistance in Lung Cancer and Colorectal Cancer Using Whole Exome Sequencing of Cell-Free DNA

“…GPR155 encodes G protein-coupled receptor 155, and reported that mutations in this gene may be associated with autism ( 59 , 60 ). Although there has been a report that GPR155 expression is suppressed in neoplasm of the thyroid, hepatocellular carcinoma, and gastric cancer, implying a tumor suppressive function for this gene, the resistant role in lung cancer, however, was not reported ( 61 , 62 ). In the COSMIC, we found that GPR155 I357S mutations were estimated as pathogenic (score 0.99) and patients with this gene alteration showed poor prognosis compared those with unaltered patients.…”