LKB1和PTEN在肝细胞癌中的表达及临床意义

Expression and clinical significance of LKB1 and PTEN in hepatocellular carcinoma

目的探讨肝激酶B1（liver kinase B1，LKB1）和张力蛋白同源基因蛋白（phosphatase and tensin homology deleted on chromosome ten, PTEN）在肝细胞癌（hepatocellular carcinoma, HCC）中的表达及其与患者预后的关系。方法免疫组化检测115例HCC患者肿瘤组织中LKB1和PTEN蛋白的表达，分析两种蛋白表达与临床病理因素的关系，应用COX比例风险模型进行多因素预后分析。结果115例肿瘤中LKB1阳性表达率仅为10．4％（12／115），PTEN阳性表达率为28．7％（33／115）：两种蛋白共表达与缺失的比例分别为5．2％（6／115）和66．1％（76／115）。LKB1与PTEN蛋白双缺失更多出现在≥50岁年龄组（χ^2=7．968，P=0．001）、中-低分化HCC（χ^2=11．297，P=0．025）以及合并脉管癌栓的HCC（χ^2=6．797，P=0．011）中。LKB1、PTEN蛋白共表达与共缺失患者的5年生存率分别为100％和36．5％（χ^2=10．969，P=0．004）。多因素COX比例风险模型分析显示，脉管癌栓、PTEN缺失和LKB1／PTEN双缺失是影响HCC预后的独立危险因素。结论LKB1／PTEN蛋白双缺失是影响HCC患者生存时间的独立危险因素。

Objective To investigate the expression of liver kinase B1 （LKB1） and phosphatase and tensin homology deleted on chromosome ten （PTEN） in hepatocellular carcinoma （HCC） and their relationship with pathological characteristics and prognosis of HCC. Methods Immunohistochemistry was used to detect expression of LKB1 and PTEN in 115 HCC cases . The relationship between clinicopathologic factors and the expressions was analyzed. Results The positive expression rate of LKB1 and PTEN was 10.4% （12/115） and 28. 7% （33/115） respectively. The coexpression ratio of LKB1 and PTEN was 5.2% （6/115）. LKB1 and PTEN double deletion rate was 66. 1% , with the latter most often found in those ≥ 50 years of age group （χ^2= 7. 968, P = 0. 001 ）, middle low differentiation HCC group （χ^2= 11. 297 ,P =0. 025） and vascular tumor thrombus group （χ^2 =6. 797 ,P =0. 011 ）. The 5 year survival rates of LKB1 and PTEN protein coexpression and double deletion patients were 100% and 36. 5% （χ^2 = 10. 969, P = 0. 004） , respectively. Multivariate COX regression analysis showed that vascular tumor thrombus, FFEN deletion and LKB1/PTEN double deletion were independent risk factors for the prognosis of HCC. Conclusions Double deletion of LKB1/PTEN protein is one of the independent factors that affect the survival time of HCC patients.