Per2对肝癌患者预后及肝癌细胞生长和凋亡的作用

Prognostic value of Per2 in hepatocellular carcinoma and its effect on the growth and apoptosis of hepatocellular carcinoma cells

目的探讨周期昼夜节律调节因子2(Per2)在肝细胞肝癌(HCC)组织中的表达和对患者生存的影响,分析Per2对肝癌SMMC-7721细胞增殖和凋亡的影响。方法应用免疫组化法检测HCC组织和癌旁肝组织中Per2的表达;对肝癌细胞系SMMC-7721转染Per2真核表达质粒后,Western blot检测Per2蛋白表达,MTS法和流式细胞计量术检测细胞增殖和凋亡。结果 117例HCC组织中,Per2阳性表达率70.94%,显著低于对应癌旁肝组织的87.18%;癌组织中Per2染色评分为2.14±1.76,显著低于癌旁肝组织的6.39±3.84(P<0.01);Per2表达与HCC患者的肿瘤直径、门脉侵袭和TNM分期相关(P<0.05);Per2低表达的患者总体生存期(OS)和无复发生存期(RFS)较Per2高表达的患者短(P<0.05)。转染Per2真核表达质粒组细胞与对照组细胞相比细胞增殖显著受抑制(P<0.05),同时细胞凋亡水平显著增加(P<0.05)。结论 HCC组织中Per2表达显著下调,Per2对肝癌的进展发挥了抑制作用,可能是通过抑制细胞增殖和促进细胞凋亡实现。

Objective To explore the expression of Per2 in hepatocellular carcinoma(HCC)and its effect on the survival of HCC patients,and to analyze the effects of Per2 on the proliferation and apoptosis of SMMC-7721 cells.Methods The protein expression of Per2 in HCC patients was analyzed by immunohistochemical(IHC)staining.SMMC-7721 cells were transfected with Per2 eukaryotic expression plasmid.The protein expression of Per2 was detected by Western blot.The cell proliferation and apoptosis was detected by MTS and flow cytometry.Results In 117 HCC tissues,the Per2 positive expression rate was 70.94%,which was significantly lower than that of 87.18%in the adjacent HCC tissue.The Per2 staining score was 2.14±1.76,which was significantly lower than that of 6.39±3.84 in the adjacent HCC tissue(P<0.01).Per2 expression was related to tumor diameter,portal vein invasion and TNM staging(P<0.05)in 117 HCC patients.The overall survival(OS)and recurrence-free survival(RFS)of HCC patients with low expression of Per2 were shorter than those with Per2 high expression(P<0.05).The cell proliferation was significantly inhibited and the apoptosis increased with the transfection of Per2 eukaryotic expression plasmid in SMMC-7721 cells(P<0.05).Conclusions The expression of Per2 in HCC is significantly reduced.Per2 inhibits the progression of HCC,possibly by inhibiting cell proliferation and promoting apoptosis.