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目的:探讨肝细胞癌(hepatocellular carcinoma,HCC)组织中缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)和脯氨酸羟化酶3(prolyl hydroxylase 3,PHD3)的表达及其临床意义。方法:应用免疫组织化学Envision二步法检测103例HCC组织、14例癌旁肝组织和13例正常肝组织中HIF-1α和PHD3的表达,并分析其与临床病理特点间的关系。结果:HIF-1α在HCC组织中的表达阳性率显著高于癌旁肝组织,其阳性表达与肿瘤最大径、脉管瘤栓、术后2年生存率、肿瘤分级和TNM分期显著相关(P<0.05)。正常肝组织不表达HIF-1α。PHD3在HCC组织中阳性表达明显高于癌旁肝组织和正常肝组织,其在HCC中阳性表达与脉管瘤栓、肿瘤分级和术后2年生存率显著相关(P<0.05)。生存分析显示,HIF-1α和PHD3阳性表达组病人术后生存期较阴性表达组明显缩短。COX多因素分析显示,HIF-1α和PHD3阳性表达是HCC的独立预后因素。结论:HIF-1α和PHD3可能在HCC的发生、发展、浸润和转移中起重要作用。对HCC中HIF-1α、PHD3表达的检测有助于判断HCC的恶性程度及预后分析。
Objective: To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and prolyl hydroxylase 3 (PHD3) in hepatocellular carcinoma (HCC) Clinical significance. Methods: The expressions of HIF-1α and PHD3 in 103 HCC tissues, 14 adjacent normal liver tissues and 13 normal liver tissues were detected by Envision immunohistochemistry. The relationship between HIF-1α and PHD3 expression was analyzed. Results: The positive expression rate of HIF-1α in HCC tissue was significantly higher than that in paracancer liver tissue. The positive expression of HIF-1α was significantly associated with the maximum tumor diameter, tumor thrombus, 2-year survival rate, tumor grade and TNM stage <0.05). Normal liver tissue does not express HIF-1α. The positive expression of PHD3 in HCC tissues was significantly higher than that in adjacent noncancerous liver tissues and normal liver tissues. The positive expression of PHD3 in HCC was significantly associated with tumor embolism, tumor grade and postoperative 2-year survival rate (P <0.05). Survival analysis showed that the survival time of HIF-1α and PHD3 positive patients was significantly shorter than that of negative ones. COX multivariate analysis showed that the positive expression of HIF-1α and PHD3 were independent prognostic factors of HCC. Conclusion: HIF-1α and PHD3 may play an important role in the occurrence, development, invasion and metastasis of HCC. The detection of HIF-1α, PHD3 expression in HCC will help to determine the degree of malignancy and prognosis of HCC.