缺氧诱导因子-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

Effect and clinical significance of hypexia-inducible factor-lα expression on cell cycle of hepatocarcinoma

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 explore the effect of hypoxia-inducible factor-1α expression on ceil cycle factors CyclinE,S-phase fraction （SPF） and its clinical significance in 62 cases of primary hepatocarcinoma. Methods The expression of was detected by using SP immunohistochemical staining and SPF was assessed by flow cytometry. Results The expression of HIF-1α,Cyclin E and SPF was correlated with tumor poor differentiation, invasive and metastasive potention and poor prognosis （Х^2 = 6.32, 3.90, 7.09;4.41,4.85,10.61. t =5.827,5.959,5.331.P〈0.05 or P〈0.01）.There was a strong association between CyclinE expression and SPF （ Х^2 = 8.85,11.78, t = 3.014, P〈 0.01）. There was also a strong association between HIF-1α expression and CyclinE or SPF （Х^2 = 4.18, t = 4. 318, P 〈 0.05 or P 〈 0.01）. Conclusion Combined detection of HIF-1α, CyclinE and SPF may be helpful to evaluate malignant degree,invasive and mentastasive potention and prognosis of hepatocarcinoma. HIF-1α could make the development of tumor by affecting G1/S transition and elevating SPF.