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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

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

Authors: Shinichi Umeda, Mitsuro Kanda, Hiroyuki Sugimoto, Haruyoshi Tanaka, Masamichi Hayashi, Suguru Yamada, Tsutomu Fujii, Hideki Takami, Yukiko Niwa, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Michitaka Fujiwara, Yasuhiro Kodera

Published in: BMC Cancer | Issue 1/2017

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Abstract

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.
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Metadata
Title
Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
Authors
Shinichi Umeda
Mitsuro Kanda
Hiroyuki Sugimoto
Haruyoshi Tanaka
Masamichi Hayashi
Suguru Yamada
Tsutomu Fujii
Hideki Takami
Yukiko Niwa
Naoki Iwata
Chie Tanaka
Daisuke Kobayashi
Michitaka Fujiwara
Yasuhiro Kodera
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3629-2

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