WWOX基因在肝细胞癌及手术切缘中的表达意义

Expression of WWOX in hepatocellular carcinoma and resection margin

目的探讨WWOX基因在肝细胞癌（HCC）和切缘中的表达状况和术后复发及预后的关系及其临床意义。方法用免疫组化方法检测76例肝癌组织及其切缘组织、20例正常肝组织中WWOX基因蛋白产物表达水平，用TUNEL法检测76例肝细胞癌的细胞凋亡水平，结合临床病理指标和术后生存率进行分析。结果WWOX基因蛋白产物在HCC中定位于细胞核，在癌旁组织中定位于细胞核与细胞浆。肝癌组织中WWOX基因蛋白表达指数为（35．2±20．1）％，低于癌旁组织和正常肝组织（P〈0．05）。并与肝癌的细胞凋亡率下降、PCNA增高、肿瘤较大、门脉分支浸润、低分化高恶性度以及术后复发等指标有关（P〈0．05）。肝癌切缘WWOX基因蛋白表达水平与术后复发率和生存率有关（P〈0．05），而与1cm以上切缘距离无关。结论肝癌组织和手术切缘存在低WWOX表达和定位异常，并可能与影响肿瘤进展、预后的生物学行为有关。肝癌组织和手术切缘WWOX表达水平测定有望成为评估肝癌进展等生物学行为和预后的有用指标之一，并有助于确定较为安全的根治切除分子切缘。

Objective To investigate the clinical significance of WWOX expression in hepatocellular carcinoma（HCC） and resection margin and explore its relation to postoperative recurrence and prognosis. Methods The expression of WWOX protein was detected with immunohistochemical method-SP in 76 cases of HCC and resection margin and 20 cases of normal liver tissues,while the apoptosis rate was detected with TUNEL method in 76 cases of HCC. The relationship between these data and clinicopathological features was analyzed with SPSS software. Results Abnormal nuclear localization of WWOX protein in HCC and nuclear/ cytoplasm localization in resection margin were detected. The WWOXLI in HCC was 35.2 % ±20.1%, lower than those of resection margin and normal liver tissues （P〈0.05）. The lower level of WWOX expression in HCC was significantly related to the lower apoptosis rate, higher PCNALI, huge tumor, cancerous thrombus in branches of portal vein, lower differentiation, lower survival rate and postoperative recurrence etc. （P〈0.05）. The WWOX expression level in resection margin was significantly related to postoperative recurrence rate （P〈0.05） but not the distance of resection margin. Conclusion The lower expression and abnormal cellular location of WWOX gene in HCC can be a frequent event, which can be related to some biological characteristics of HCC to influence its progress and prognosis. The expression level of WWOX gene in HCC and resection margin may be one of useful indicators in forecasting the progress and prognosis and be used as a safe biomarker of molecular margin.