Regulator of G‑protein signaling 5 enhances portal vein invasion in hepatocellular carcinoma

Umeno,Yumi; Ogasawara,Sachiko; Akiba,Jun; Hattori,Satoshi; Kusano,Hironori; Nakashima,Osamu; Koga,Hironori; Torimura,Takuji; Yamakawa,Ryoji; Yano,Hirohisa

doi:10.3892/ol.2017.7474

Regulator of G‑protein signaling 5 enhances portal vein invasion in hepatocellular carcinoma

Authors:
- Yumi Umeno
- Sachiko Ogasawara
- Jun Akiba
- Satoshi Hattori
- Hironori Kusano
- Osamu Nakashima
- Hironori Koga
- Takuji Torimura
- Ryoji Yamakawa
- Hirohisa Yano
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Affiliations: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Biostatistic Center, Kurume University, Kurume, Fukuoka 830‑0011, Japan, Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Fukuoka 830‑0011, Japan, Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: November 23, 2017 https://doi.org/10.3892/ol.2017.7474
Pages: 1763-1770

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Abstract

Portal vein invasion (PVI) is a major prognostic factor in hepatocellular carcinoma (HCC). The aim of the present study was to identify molecules that regulate PVI. Sections of cancerous tissue, paired noncancerous tissue and the PVI area were collected from 3 frozen HCC sections, using laser microdissection. The present study focused on 3 upregulated molecules, integrin β3 (ITGB3), secreted phosphoprotein 1 (SPP1) and regulator of G‑protein signaling 5 (RGS5), and 2 molecules that were downregulated in PVI tissue compared with cancer tissue, metallothionein 1G (MT1G) and metallothionein 1H (MT1H), as determined by cDNA microarray analysis. Reverse transcription‑quantitative polymerase chain reaction analysis of 32 HCC cases revealed that RGS5 mRNA levels were significantly increased and MT1 G and MT1H mRNA levels were significantly decreased in cancerous tissue compared with noncancerous tissue. However, there was no significant difference in ITGB3 and SPP1 expression. There were no significant differences between the expression of these molecules and any clinicopathologic factors, including PVI. Immunohistochemical staining for RGS5 in 60 HCC cases demonstrated that RGS5 protein levels were higher in cancerous tissue compared with paired noncancerous tissue in 63.3% of HCC cases. Furthermore, high expression of RGS5 in cancerous tissue was significantly associated with PVI and tended to be associated with intrahepatic metastasis. Confluent multinodular type was significantly more frequent in cases with high expression of RGS5 in the cancerous tissue. Therefore, RGS5 may be a useful prognostic biomarker as well as a potential target of molecular therapy to treat HCC.

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