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

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 signa...

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Autores principales: Umeda, Shinichi, Kanda, Mitsuro, Sugimoto, Hiroyuki, Tanaka, Haruyoshi, Hayashi, Masamichi, Yamada, Suguru, Fujii, Tsutomu, Takami, Hideki, Niwa, Yukiko, Iwata, Naoki, Tanaka, Chie, Kobayashi, Daisuke, Fujiwara, Michitaka, Kodera, Yasuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580443/
https://www.ncbi.nlm.nih.gov/pubmed/28863781
http://dx.doi.org/10.1186/s12885-017-3629-2
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author Umeda, Shinichi
Kanda, Mitsuro
Sugimoto, Hiroyuki
Tanaka, Haruyoshi
Hayashi, Masamichi
Yamada, Suguru
Fujii, Tsutomu
Takami, Hideki
Niwa, Yukiko
Iwata, Naoki
Tanaka, Chie
Kobayashi, Daisuke
Fujiwara, Michitaka
Kodera, Yasuhiro
author_facet Umeda, Shinichi
Kanda, Mitsuro
Sugimoto, Hiroyuki
Tanaka, Haruyoshi
Hayashi, Masamichi
Yamada, Suguru
Fujii, Tsutomu
Takami, Hideki
Niwa, Yukiko
Iwata, Naoki
Tanaka, Chie
Kobayashi, Daisuke
Fujiwara, Michitaka
Kodera, Yasuhiro
author_sort Umeda, Shinichi
collection PubMed
description 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.
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spelling pubmed-55804432017-09-07 Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma Umeda, Shinichi Kanda, Mitsuro Sugimoto, Hiroyuki Tanaka, Haruyoshi Hayashi, Masamichi Yamada, Suguru Fujii, Tsutomu Takami, Hideki Niwa, Yukiko Iwata, Naoki Tanaka, Chie Kobayashi, Daisuke Fujiwara, Michitaka Kodera, Yasuhiro BMC Cancer Research Article 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. BioMed Central 2017-09-01 /pmc/articles/PMC5580443/ /pubmed/28863781 http://dx.doi.org/10.1186/s12885-017-3629-2 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Umeda, Shinichi
Kanda, Mitsuro
Sugimoto, Hiroyuki
Tanaka, Haruyoshi
Hayashi, Masamichi
Yamada, Suguru
Fujii, Tsutomu
Takami, Hideki
Niwa, Yukiko
Iwata, Naoki
Tanaka, Chie
Kobayashi, Daisuke
Fujiwara, Michitaka
Kodera, Yasuhiro
Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title_full Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title_fullStr Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title_full_unstemmed Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title_short Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
title_sort downregulation of gpr155 as a prognostic factor after curative resection of hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580443/
https://www.ncbi.nlm.nih.gov/pubmed/28863781
http://dx.doi.org/10.1186/s12885-017-3629-2
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