Hippo信号通路相关蛋白对肝癌肝移植术后肿瘤复发的影响

Effects of Hippo pathway component on tumor recurrence after liver transplantation

    摘要
  • 摘要: 目的：检测Hippo信号通路相关蛋白在肝癌组织中的表达，探讨其对肝癌肝移植术后肿瘤复发的影响。
    方法：回顾性分析2004年7月至2009年9月广州中山大学附属第三医院收治的105例肝癌患者的临床资料。收集施行同种异体肝移植、经组织病理学检查证实为肝细胞癌患者的手术切除标本、肿瘤数目、肿瘤直径、肿瘤侵犯血管情况、术前AFP水平、术后病理检查结果等临床病理资料。通过门诊、信件和电话等方式对患者进行术后随访，肝移植术后1个月内每周随访1次，半年内每个月随访1次，1年后每3个月随访1次。随访时间截至2012年12月，以首次观察到患者肿瘤复发为终点，无瘤生存时间以手术日期至发现患者肿瘤复发为终点。免疫组织化学染色检测肝癌组织中YAP和磷酸化YAP蛋白、Hippo信号通路核心蛋白(Lats1/2、磷酸化Lats1/2、Mst1、磷酸化Mst1/2)的表达。计数资料采用 χ 2检验，连续资料采用 Student t 检验，对影响肝癌肝移植术后患者无瘤生存时间的因素进行单因素及多因素分析采用COX比例风险模型，KaplanMeier法绘制生存曲线，Log rank检验分析患者无瘤生存情况。
    结果：YAP和磷酸化YAP蛋白在肝癌组织中的阳性表达主要定位于细胞核及细胞质，Lats1/2、磷酸化Lats1/2、Mst1、磷酸化Mst1/2蛋白主要定位于细胞质。YAP和磷酸化YAP蛋白阳性表达率为51.43%(54/105)和55.24%(58/105)， Lats1/2、磷酸化Lats1/2、Mst1、磷酸化Mst1/2蛋白阳性表达率分别为45.71%(48/105)、9.52%(10/105)、64.76%(68/105)和20.00%(21/105)。YAP蛋白阳性表达与肿瘤直径、静脉大血管侵犯及肝癌AJCC分期有关( χ 2=4.129，P <0.05)。单因素分析结果表明：YAP蛋白表达、Lats1/2蛋白表达、磷酸化Mst1/2蛋白表达、年龄、肿瘤直径、组织分化程度、术前AFP水平、静脉大血管侵犯、肝癌AJCC分期是影响患者肝移植术后肿瘤复发的危险因素( HR=2.603，0.502，1.802，0.955，3.559，2.395，2.414，2.915，2.086，95%可信区间：1.452～4.666，0.287～0.880，1.040～3.123，0.931～0.981，1.921～6.595，1.475～3.889，1.313～4.337，1.604～5.229，1.370～3.176，P< 0.05)。多因素分析结果表明：YAP蛋白阳性表达、肿瘤直径>5 cm、组织低分化、肝癌AJCC Ⅲ期是影响患者肝移植术后肿瘤复发的独立危险因素( HR=2.011，2.176，2.390，1.574，95%可信区间：1.115～3.628，1.125～4.206，1.448～3.945，1.041～2.381，P< 0.05)。患者中位随访时间为13.0个月(1.0～96.0个月)，失访8例，54例患者肿瘤复发，复发时间为1.0～41.0个月，平均复发时间为6.7个月。YAP蛋白阳性表达者与YAP蛋白阴性表达者比较肝移植术后无瘤生存时间明显缩短(Logrank值=12.890， P <0.05)。
    结论：YAP和磷酸化YAP蛋白在肝癌组织中的阳性表达主要定位于细胞核及细胞质，Lats1/2、磷酸化Lats1/2、Mst1、磷酸化Mst1/2蛋白阳性表达主要定位于细胞质。Hippo信号通路中，只有YAP蛋白阳性表达是肝癌患者肝移植术后肿瘤复发的独立危险因素。

     

    Abstract: Objective:To investigate the expression of Hippo pathway component in hepatic cancer tissues and investigate its effects on the tumor recurrence after liver transplantation.
    Methods:The clinical data of 105 patients with liver cancer who were admitted to the Third Affiliated Hospital of Sun Yat Sen University from July 2004 to September 2009 were retrospectively analyzed. The samples of liver cancer tissues were collected. The maximum diameter, number of foci, blood vessel involvement, preoperative level of alpha fetoprotein (AFP), results of postoperative pathological examination were analyzed. All the patients were followed up via out patient examination, mail and phone call. Patients were followed up once a week within the first month after operation, and once a month within the 6 months after operation, and then once every 3 months at 1 year later. The follow up ended in December 2012 or tumor recurrence. The disease free survival time began at the date of operation and ended at the time of tumor recurrence. The expressions of Yes associated protein (YAP), phosphorylated YAP, Hippo pathway component (Lats1/2, pLats1/2, Mst1, pMst1/2) were detected by immunohistochemical staining. All data were analyzed using the chi square test or Student t test. Factors might influence the postoperative tumor free survival time after liver transplantation were analyzed using the Cox regression model. The survival curve was drawn by Kaplan Meier method, and the disease free survival was analyzed using Log rank test.
    Results:Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm, and the positive expressions of Lats1/2, pLats1/2, Mst1 and pMst1/2 were detected in the cytoplasm. The positive expressions of YAP, phosphorylated YAP, Lats1/2, pLats1/2, Mst1 and pMst1/2 protein were 51.43%(54/105), 55.24%(58/105), 45.71%(48/105), 9.52%(10/105), 64.76%(68/105) and 20.00%(21/105), respectively. The positive expression of YAP was correlated with the tumor diameter, venous infiltration and AJCC stage ( χ 2-41.0 months). The disease free survival time of patients with positive expression of YAP were significantly shorter than those with negative expression of YAP (Log rank value=12.890, P <0.05).
    Conclusions: Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm, and the positive expressions of Lats1/2, pLats1/2, Mst1 and pMst1/2 were detected in the cytoplasm. The positive expression of YAP is the independent risk factor for tumor recurrence after liver transplantation.

     

    • HTML全文
    • 参考文献(0)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回