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目的:探讨胰腺癌中E3泛素连接酶亚单位Ring1B、组蛋白赖氨酸特异性去甲基化酶1(LSD1)及细胞周期调节因子P16表达与及其与患者预后的关系。方法:用免疫组化法检测85例胰腺癌患者手术标本(癌组织与癌旁组织)中LSD1、Ring1B与P16蛋白的表达及分布,并选取其中6对癌组织和癌旁组织,用qRT-PCR和Western blot法检测mRNA和蛋白表达;分析三者在胰腺癌组织中表达的相关性,及其与患者生存的关系。结果:免疫组化结果显示,Ring1B与LSD1蛋白主要表达于细胞浆,P16主要表达于胞核;Ring1B与LSD1在胰腺癌组织中表达明显高于癌旁组织,而P16的表达明显低于癌旁组织(均P<0.05);在胰腺癌组织中Ring1B、LSD1的表达与P16的表达均呈负相关(r=-476;r=-0.673,均P<0.05)。qRTPCR结果显示,胰腺癌组织中Ring1B和LSD1的mRNA的平均相对表达量均明显高于癌旁组织(8.908vs.1.947;7.126 vs.1.940,均P<0.05),P16的mRNA的平均相对表达量明显低于癌旁组织(1.269vs.5.237,P<0.05);Western blot结果显示,三者的蛋白表达趋势与mRNA表达一致。生存分析显示,Ring1B、LSD1高表达患者生存率均分别低于其低表达患者(χ~2=8.958,P=0.012;χ~2=8.856,P=0.010),而P16高表达患者生存率高于其低表达患者(χ~2=7.867,P=0.024)。结论:胰腺癌组织中Ring1B与LSD1表达升高,P16表达降低;Ring1B、LSD1可能分别通过组蛋白泛素化和去甲基化调控P16的表达,从而影响胰腺癌预后。
Objective: To investigate the expression of E3 ubiquitin ligase subunits Ring1B, histone lysine-specific demethylase 1 (LSD1) and cell cycle regulators P16 in pancreatic cancer and its relationship with prognosis. Methods: The expression and distribution of LSD1, Ring1B and P16 proteins in 85 cases of pancreatic cancer specimens were detected by immunohistochemistry, and 6 pairs of cancer tissues and adjacent tissues were selected. The expression of qRT- PCR and Western blot were used to detect the mRNA and protein expression. The correlation between the three expression in pancreatic cancer and their relationship with the survival of patients were analyzed. Results: The results of immunohistochemistry showed that the expression of Ring1B and LSD1 protein was mainly in the cytoplasm, while the expression of P16 was mainly in the nucleus. The expression of Ring1B and LSD1 in pancreatic cancer tissues was significantly higher than that in paracancerous tissues, while the expression of P16 was significantly lower than that in adjacent tissues (All P <0.05). The expressions of Ring1B and LSD1 in pancreatic cancer tissues were negatively correlated with the expression of P16 (r = -476; r = -0.673, all P <0.05). The results of qRTPCR showed that the average relative expression of mRNA of Ring1B and LSD1 in pancreatic cancer tissues was significantly higher than that in paracancer tissues (8.908 vs.1.947; 7.126 vs.1.940, all P <0.05). The mean relative mRNA expression of P16 (1.269 vs.5.237, P <0.05). The result of Western blot showed that the expression of all three proteins was consistent with the mRNA expression. Survival analysis showed that the survival rates of patients with high expression of Ring1B and LSD1 were lower than those with low expression (χ ~ 2 = 8.958, P = 0.012, χ ~ 2 = 8.856, P = 0.010) In its low expression of patients (χ ~ 2 = 7.867, P = 0.024). Conclusions: The expressions of Ring1B and LSD1 in pancreatic cancer tissues are elevated and the expression of P16 is decreased. The expression of P16 may be regulated by histone ubiquitination and demethylation respectively, which may affect the prognosis of pancreatic cancer.