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

Abstract

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.

Expression and role of regulator of G‐protein signaling 5 in squamous cell carcinoma of the tongue

“…In this study, we found that RGS5 appears to be involved in the aggressive biological features of OSCC, which can be mediated by properties (Huang et al, 2012;Wang et al, 2010). In contrast, high RGS5 expression in HCC was reported to be associated with various aggressive properties, such as vascular invasion, intrahepatic metastasis, and EMT (Hu et al, 2013;Umeno et al, 2018). These reports indicate that the role of RGS5 in carcinoma is organ specific.…”

“…Hu et al (2013) reported that regulator of G-protein signaling (RGS) 5 is related with tumor invasion by inducing EMT of hepatocellular carcinoma (HCC) cells. We also demonstrated that RGS5 expression is closely related with portal vein invasion and intrahepatic metastasis in HCC (Umeno et al, 2018). The RGS family is a group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (Hurst & Hooks, 2009).…”

“…In gastric carcinoma and nonsmall cell lung carcinoma, RGS5 expression was positively correlated with tumor differentiation, and low RGS5 expression was associated with aggressive properties (Huang et al, ; Wang et al, ). In contrast, high RGS5 expression in HCC was reported to be associated with various aggressive properties, such as vascular invasion, intrahepatic metastasis, and EMT (Hu et al, ; Umeno et al, ). These reports indicate that the role of RGS5 in carcinoma is organ specific.…”

“…NBP2‐00880; dilution, 1:250; Novus Biologicals, LLC, Littleton, CO, USA). For the RGS5 profile, we evaluated cytoplasmic staining as described by Umeno et al (). Normal pancreatic islets of Langerhans were used as positive control for RGS5.…”

“…NBP2-00880; dilution, 1:250; Novus Biologicals, LLC, Littleton, CO, USA). For the RGS5 profile, we evaluated cytoplasmic staining as described by Umeno et al (2018). This automated system uses the streptavidin-biotin complex method with 3,3′-diaminobenzidine as a chromogenic substrate (Ventana iVIEW DAB Detection Kit).…”