骨桥蛋白、血管内皮生长因子-A和乏氧诱导因子-1α在肝细胞癌中的表达及意义

Differential expression of OPN,VEGF-A,and HIF-1α and its clinical significance in hepatocellular carcinoma

目的探讨骨桥蛋白(OPN)、血管内皮生长因子-A(VEGF-A)和乏氧诱导因子(HIF)-1α在肝细胞癌(HCC)中的表达及临床意义。方法采用免疫组织化学法检测肝癌组(90例)、癌旁肝硬化组(20例)及正常组(15例)中OPN、VEGF-A和HIF-1α的表达。结果 OPN、VEGF-A和HIF-1α在HCC组呈明显高表达,阳性率分别为76.67%(69/90)、71.11%(64/90)和73.33%(66/90)。其中OPN、VEGF-A显著高于癌旁肝硬化组及正常组,HIF-1α在HCC组的表达与肝硬化组无差异,与正常组有显著差异。OPN、VEGF-A、HIF-1α的表达与肝癌的临床病理特征如癌栓形成、包膜完整性、肿瘤分化和分期、肿瘤转移等有相关性(P<0.05),三者之间表达呈正相关性(P<0.05)。结论 OPN、VEGF-A、HIF-1α在肝癌中高表达,联合检测有助于判断肝癌的生物学特征,为肝癌的分子靶向治疗提供重要的可能靶点。

Objective To investigate the expression patterns of osteopontin （ OPN）, vascular endothelial growth factor - A （ VEGF - A）, and hypoxia-inducible factor-1α（ HIF- 1α） in primary hepatocellular carcinoma （HCC） and determine the clinical significance of this differential expression profile. Methods Immunohistochemical staining of OPN, VEGF - A, and HIF - 1 α was carried out on primary HCC tissues from 90 patients, HCC - adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Corre- lations between expression levels and HCC clinicopathological characteristics were assessed by Spearman＇s correlation coefficient. Results The majority of HCC tissues showed positive immunostaining for OPN （69/90, 76.67% ）, VEGF - A （64/90, 71.11% ）, and HIF - 1α （66/90, 73.33% ）. OPN - and VEGF -A -positivity were significantly higher than the results from the cirrhosis tissues and normal tis- sues. HIF -1α -positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF - A, and HIF - 1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis （P 〈 0.05 ）. Conclusion HCC tissues overexpress OPN, VEGF - A, and HIF - 1 ot and this dif- ferential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.