Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients.
Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients.
复制标题
肝细胞癌中组织蛋白酶B的过度表达预示着HCC患者的不良预后
DOI：
10.1186/s12943-016-0503-9
复制
发表时间：
2016-02-20
期刊：
影响因子：
37.3
通讯作者：
Luo R
中科院分区：
文献类型：
--
作者：
Ruan J;Zheng H;Rong X;Rong X;Zhang J;Fang W;Zhao P;Luo R
背景多项研究发现组织蛋白酶 B (CTSB) 在许多肿瘤类型中表达上调，并促进肿瘤进展。然而，CTSB 在肝细胞癌 (HCC) 进展中的作用仍不清楚。本研究旨在通过大量样本和细胞系（MHCC-97H和MHCC-97L）研究CTSB在HCC中的表达和作用，并评估CTSB蛋白在HCC患者中的临床和预后意义。方法通过Western-blotting、Real-time PCR和免疫组化检测CTSB在HCC组织和细胞系中的表达。 染色。采用伤口愈合实验和侵袭实验验证CTSB对HCC细胞系迁移和侵袭能力的影响。采用裸鼠成瘤实验分析CTSB对HCC细胞系致瘤性的影响。结果CTSB蛋白在癌组织中的表达水平远高于癌旁组织。 CTSB高表达组患者的总生存期显着短于CTSB低表达组。 CTSB 高表达与晚期临床分期、组织学分级和肿瘤复发显着相关。体外和体内实验表明，MHCC-97 L 细胞中 CTSB 的过度表达可促进细胞侵袭和肿瘤进展能力。 MHCC-97H 中 CTSB 的下调显示出相反的效果。 CTSB 敲低或过度表达引起的这些表型变化与基质金属肽酶 MMP-9 的表达相关。此外，多变量分析提示CTSB表达可能是HCC患者根治性手术后生存的独立预后指标。结论CTSB可能作为癌基因参与HCC的发生和发展，因此可能是HCC患者有价值的预后标志物。
BackgroundSeveral studies have found that Cathepsin B (CTSB) is up-regulated in many tumor types and facilitates tumor progression. However, the role of CTSB in hepatocellular carcinoma (HCC) progression remains unclear. This study was aimed at investigating the expression and role of CTSB in HCC in a large set of samples and cell lines (MHCC-97H and MHCC-97 L), and evaluating the clinical and prognostic significance of CTSB protein in patients with HCC.MethodsThe expression of CTSB was examined in HCC tissue and cell lines by Western-blotting, Real-time PCR, and immunohistochemical staining. Wound healing assay and invasion assay were used to verify the effect of CTSB on the migration and invasion ability of HCC cell lines. Tumor formation assay in nude mice was used to analyze the effect of CTSB on the tumorigenicity of HCC cell lines.ResultsThe status of CTSB protein in carcinoma tissues is much higher than that in paracarcinoma tissues. The overall survival of the patients with high CTSB expression was significantly shorter than the low CTSB expression group. High CTSB expression was significantly correlated with advanced clinical staging, histological grade, and tumor recurrence. In vitro and in vivo experiments demonstrated that over-expression of CTSB in MHCC-97 L cells promoted cell invasion and tumor progression ability. Down-regulation of CTSB in MHCC-97H showed the opposite effects. These phenotypic changes caused by CTSB knockdown or over-expression correlated with expression of the matrix metallopeptidase MMP-9. Moreover, multivariate analysis suggested that CTSB expression might be an independent prognostic indicator for the survival of HCC patients after curative surgery.ConclusionsCTSB might be involved in the development and progression of HCC as an oncogene, and thereby may be a valuable prognostic marker for HCC patients.