Kuang Xuejun, Zhu Jiye, Peng Zhao, Wang Jianjun, Chen Zhigang
Department of Clinical Medicine, Xiangnan University, Chenzhou, 423000, China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Xiangnan University, Chenzhou, 423000, China.
Dig Dis Sci. 2016 Feb;61(2):489-500. doi: 10.1007/s10620-015-3879-2. Epub 2015 Sep 19.
Recent studies have demonstrated that transducin (beta)-like 1 X-linked receptor 1 (TBLR1) is involved in tumor progression. However, the exact role and clinical significance of TBLR1 in hepatocellular carcinoma (HCC) are poorly understood.
In this study, we aimed to investigate the expression and clinical significance of TBLR1 in HCC.
Quantitative polymerase chain reaction and immunohistochemical staining were performed to detect the expression levels of TBLR1 in HCC tissue and adjacent noncancerous tissue (ANT). The relationships between TBLR1 expression and clinicopathological factors were examined in this study. The effects of TBLR1 on epithelial-mesenchymal transition (EMT) of HCC cells were investigated in vitro.
The expression levels of TBLR1 were elevated in HCC cell lines. TBLR1 mRNA in HCC tissue was markedly higher (P < 0.001) than that in ANT. High expression of TBLR1 is closely related to serum alpha fetoprotein (P = 0.047), BCLC stage (P < 0.001), maximum size of tumors (P < 0.001), tumor embolus (P < 0.001), and histological grade (P < 0.001). The disease-free survival and overall survival of HCC patients with high expression of TBLR1 were significantly shorter. Furthermore, we found that EMT of HCC cells could be induced by up-regulating TBLR1 and be inhibited by down-regulating TBLR1. ICG-001, the inhibitor of Wnt/β-catenin signaling, could suppress induction of EMT mediated by TBLR1.
Our finding suggested that TBLR1 is likely to be a potential prognostic indicator and therapeutic target for HCC and that TBLR1 may be implicated in EMT of HCC cells.
近期研究表明,转导素(β)样 1 X 连锁受体 1(TBLR1)参与肿瘤进展。然而,TBLR1 在肝细胞癌(HCC)中的确切作用和临床意义尚不清楚。
本研究旨在探讨 TBLR1 在 HCC 中的表达及临床意义。
采用定量聚合酶链反应和免疫组织化学染色检测 HCC 组织及癌旁非癌组织(ANT)中 TBLR1 的表达水平。本研究检测了 TBLR1 表达与临床病理因素之间的关系。体外研究了 TBLR1 对 HCC 细胞上皮-间质转化(EMT)的影响。
HCC 细胞系中 TBLR1 的表达水平升高。HCC 组织中 TBLR1 mRNA 明显高于 ANT(P < 0.001)。TBLR1 的高表达与血清甲胎蛋白(P = 0.047)、BCLC 分期(P < 0.001)、肿瘤最大径(P < 0.001)、肿瘤栓子(P < 0.001)及组织学分级(P < 0.001)密切相关。TBLR1 高表达的 HCC 患者无病生存期和总生存期明显缩短。此外,我们发现上调 TBLR1 可诱导 HCC 细胞发生 EMT,而下调 TBLR1 则可抑制其发生。Wnt/β-连环蛋白信号通路抑制剂 ICG-001 可抑制 TBLR1 介导的 EMT 诱导。
我们的研究结果表明,TBLR1 可能是 HCC 的潜在预后指标和治疗靶点,且 TBLR1 可能参与 HCC 细胞的 EMT 过程。