Umeno Yumi, Ogasawara Sachiko, Akiba Jun, Hattori Satoshi, Kusano Hironori, Nakashima Osamu, Koga Hironori, Torimura Takuji, Yamakawa Ryoji, Yano Hirohisa
Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Oncol Lett. 2018 Feb;15(2):1763-1770. doi: 10.3892/ol.2017.7474. Epub 2017 Nov 23.
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.
门静脉侵犯（PVI）是肝细胞癌（HCC）的一个主要预后因素。本研究的目的是鉴定调控PVI的分子。使用激光显微切割技术从3个冷冻的HCC切片中收集癌组织、配对的非癌组织和PVI区域的切片。本研究聚焦于3个上调分子，整合素β3（ITGB3）、分泌磷蛋白1（SPP1）和G蛋白信号调节因子5（RGS5），以及2个在PVI组织中相对于癌组织下调的分子，金属硫蛋白1G（MT1G）和金属硫蛋白1H（MT1H），这是通过cDNA微阵列分析确定的。对32例HCC病例进行的逆转录定量聚合酶链反应分析显示，与非癌组织相比，癌组织中RGS5 mRNA水平显著升高，MT1G和MT1H mRNA水平显著降低。然而，ITGB3和SPP1的表达没有显著差异。这些分子的表达与任何临床病理因素（包括PVI）之间均无显著差异。对60例HCC病例进行的RGS5免疫组织化学染色显示，在63.3%的HCC病例中，癌组织中的RGS5蛋白水平高于配对的非癌组织。此外，癌组织中RGS5的高表达与PVI显著相关，并倾向于与肝内转移相关。在癌组织中RGS5高表达的病例中，融合多结节型明显更常见。因此，RGS5可能是一种有用的预后生物标志物，也是治疗HCC的分子治疗的潜在靶点。
