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目的探讨缺氧诱导因子(HIF)-1α在肝癌中的表达及其对肿瘤细胞周期的影响和临床意义。方法采用免疫组织化学SP法检测62例肝癌标本中HIF-1α和Cyclin E的表达,同时应用流式细胞仪对S期细胞比(SPF)进行检测。结果随着肝癌分化程度的降低,出现门脉/胆管浸润或发生淋巴结/远处转移,HIF-1α、CyclinE阳性表达率增加,SPF值也升高(x~2值分别为6．32、3．90、7．09；4．41、4．85、10．61,t值分别为5．827、5．959、5．331,P＜0．05或P＜0．01)；在短、中期生存患者中,三者也高于长期生存者(x~2值分别为8．85、11．78；t值为3．014,P均＜0．01)。Cyclin E阳性表达病例SPF值高于其阴性表达者(t值为4．191,P＜0．01)。HIF-1α表达与Cyclin E表达、SPF值呈明显相关(x~2值为4．18,t值为4．318,P＜0．05或P＜0．01)。结论三者的检测对判断肝癌的恶性程度、侵袭转移能力及预后具有重要的临床意义。在肝癌中,HIF-1α可能通过影响肿瘤细胞G_1/S调控点(CyclinE调控),SPF值升高从而促进肿瘤的进展。
Objective To investigate the expression of hypoxia inducible factor (HIF) -1α in hepatocellular carcinoma (HCC) and its effect on tumor cell cycle and its clinical significance. Methods The expression of HIF-1α and Cyclin E in 62 specimens of hepatocellular carcinoma was detected by immunohistochemical SP method, and the S phase cell ratio (SPF) was detected by flow cytometry. Results With the decrease of the degree of differentiation of HCC, the positive rate of HIF-1α and CyclinE increased and the value of SPF increased (P <0.05), and the portal vein / bile duct infiltration or lymph node / distant metastasis occurred .90,7.09; 4.41,4.85,10.61, t values were 5.827,5.959,5.331, P <0.05 or P <0.01); in the short Among the patients with mid-term survival, the three were also higher than those with long-term survival (x ~ 2 values were 8.85 and 11.78 respectively; t = 3.014, P <0.01). The SPF value of Cyclin E positive expression was higher than that of negative expression (t = 4.191, P <0.01). The expression of HIF-1α was significantly correlated with the expression of Cyclin E and SPF (x ~ 2 = 4.18, t = 4.318, P <0.05 or P <0.01). Conclusion The detection of the three has important clinical significance in judging the malignant degree, invasion and metastasis ability and prognosis of hepatocellular carcinoma. In HCC, HIF-1αpromote tumor progression by affecting G_1 / S regulatory (CyclinE) regulation of tumor cells and increasing SPF.