骨膜蛋白对肝癌细胞侵袭转移和肝癌预后的影响

Effects of periostin on hepatocellular carcinoma cells invasion, metastasis and prognosis

目的探究骨膜蛋白(POSTN)在肝癌组织中的表达水平与其预后的关系以及其在肝癌侵袭、转移中的作用。方法通过实时荧光定量核酸扩增技术(QPCR)和免疫组织化学(IHC)的方法检测肝癌组织POSTN的表达水平;应用Kaplan-Meier法和Log-rank检验分析POSTN表达水平和肝癌患者术后预后的关系;在体外实验中检测POSTN在不同转移特性的肝癌细胞中的表达,并通过质粒转染技术介导POSTN在低转移特性肝癌细胞中过表达,利用Transwell细胞迁移实验和Matrigel细胞侵袭实验观察POSTN对肝癌细胞侵袭和转移的影响。POSTN的表达水平的比较用t检验分析。结果组织中POSTN的表达水平从高到低依次是转移性肝癌组织、非转移性肝癌组织和正常肝组织(P = 0.006)。POSTN高表达组的肝癌患者术后中位生存时间和3年生存率均显著低于低表达组(10.00个月,44.44%;59.00个月,53.13%,P = 0.0312)。在体外实验中,与低、中转移特性的Huh7、MHCC97L细胞相比,高转移特性的MHCC97H细胞中POSTN的表达最高;在MHCC97L细胞中过表达POSTN后,MHCC97L细胞的迁移和侵袭能力增加。结论POSTN与肝癌的转移和侵袭等病理过程相关,可促进肝癌细胞的迁移和侵袭,有望成为肝癌患者术后预后和复发的重要生物学标志物和抑制转移发生的治疗靶标。

Objective To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis. Methods The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test. Results The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%;59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased. Conclusion POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.