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肝细胞肝癌组织c-Met、Fascin及CD44表达与临床病理特征及预后的相关性

Associations of c-Met, Fascin and CD44 with clinical pathological features and prognosis of patients with hepatocellular carcinoma

    摘要
  • 摘要:
    目的 探讨肝细胞肝癌（hepatocelluar carcinoma，HCC）中c-Met、Fascin及CD44的表达与临床病理特征及预后之间的关系。
    方法 从癌症基因组图谱（the cancer genome atlas，TCGA）数据库下载HCC中c-Met、Fascin及CD44的RNA SEqV2资料，比较50例HCC组织和对应癌旁肝组织中三者的表达。采用蛋白质印迹法分别检测6例新鲜HCC及对应癌旁肝组织中c-Met、Fascin及CD44的蛋白表达。通过免疫组织化学法（immunohistochemistry，IHC）检测186例HCC患者中HCC组织及癌旁组织c-Met、Fascin及CD44蛋白的表达，分析三者与临床病理特征及预后的关系。
    结果 TCGA显示，HCC组织中c-Met、Fascin及CD44的mRNA表达较癌旁肝组织升高（P < 0.01）。蛋白质印迹显示，新鲜HCC组织中c-Met、Fascin及CD44蛋白表达水平均高于癌旁肝组织（P < 0.05）。IHC显示，186例HCC患者癌组织及癌旁组织中，c-Met蛋白表达阳性率分别为60.2%（112/186）和32.8%（61/186），Fascin蛋白表达阳性率分别为56.5%（105/186）和24.7%（46/186），CD44蛋白表达阳性率分别为73.1%（136/186）和50.5%（94/186），3种蛋白在HCC组织中的表达均高于癌旁组织（P < 0.01）。c-Met、Fascin及CD44蛋白在脉管侵犯、低分化及术后复发患者癌组织表达中均增加（P < 0.05）。Spearman相关性分析显示，c-Met与Fascin的表达正相关（r=0.349 5，P < 0.001）。Kaplan-Meier生存分析及多因素Cox回归分析显示，c-Met、Fascin及CD44表达是影响HCC患者生存的危险因素（P < 0.05）。
    结论 c-Met、Fascin及CD44的mRNA和蛋白表达水平在HCC组织中均升高，在脉管侵犯、肿瘤低分化及复发患者HCC组织中水平更高，且为HCC患者生存的独立危险因素。

     

    Abstract:
    Objective To explore the association of c-Met, Fascin and CD44 with the clinical pathological fetures and prognosis of patients with hepatocellular carcinoma (HCC).
    Methods The RNA SEqV2 data of c-Met, Fascin and CD44 in HCC from the cancer genome atlas (TCGA) were downloaded (n=50). The mRNA levels of c-Met, Fascin and CD44 between cancer and paracancer tissues were compared. Western blotting was used to detect the expression levels of c-Met, Fascin and CD44 proteins in 6 cases of cancer and the matched paracancer liver tissues. The expression levels of c-Met, Fascin and CD44 proteins were examined in cancer and paracancer liver tissues from 186 patients by immunohistochemistry (IHC). The associations of c-Met, Fascin and CD44 with clinical pathological factors and prognosis of patients were analyzed.
    Results The data from TCGA showed that the mRNA levels of c-Met, Fascin and CD44 were significantly higher in cancer tissues than those in the paracancer tissues (P < 0.01). Western blotting results showed that the protein levels of c-Met, Fascin and CD44 in fresh cancer tissues were significantly higher than those in the paracancer tissues (P < 0. 05). IHC results showed the c-Met expressed in 60.2% (112/186) of cancer tissues and 32.8% (61/186) of paracancer tissues, Fascin expressed in 56.5% (105/186) of cancer tissues and 24.7% (46/186) of paracancer tissues, and CD44 expressed in 73.1% (136/186) of cancer tissues and 50.5% (94/186) of paracancer tissues. The protein levels of c-Met, Fascin and CD44 in cancer tissues were higher than those in paracancer tissues (P < 0.01). The expressions of c-Met, Fascin and CD44 proteins in patients with vascular invasion or poor differentiation tumor and in recurrence patients were higher (P < 0.05). Spearman analysis showed that there was a positive correlation between c-Met and Fascin (r=0.349 5, P < 0.001). Kaplan-Meier and multivariate Cox analysises all showed that higher levels of c-Met, Fascin and CD44 were risk factors for HCC patients survival (P < 0.05).
    Conclusion c-Met, Fascin and CD44 expressions are increased in HCC cancer tissues, are higher in vascular invasion, lower tumor differentiation, and recurrence patients, and may be independent risk factors for HCC prognosis.

     

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