Nedd4L对前列腺癌患者TrkA抑癌性泛素化的影响研究

Effect of Nedd4L on TrkA Ubiquitination in Patients with Prostate Cancer

目的探讨Nedd4L对前列腺癌患者Trk A抑癌性泛素化的影响。方法采用荧光定量PCR法,检测60例前列腺癌组织(PC组)及24例前列腺良性增生组织(BPH组)中Nedd4L及Trk A的水平,分析Nedd4L和Trk A的相关性,同时分析NEDD4L和Trk A的水平分别与前列腺癌临床特征(年龄、Gleason评分、TNM分期)的关系。采用免疫印迹法进一步检测Trk A蛋白水平和Trk Ade泛素化水平。结果 1PC组Nedd4L的mRNA水平显著低于BPH组Nedd4L的mRNA水平(t=13.01,P<0.0001);PC组Trk A mRNA水平明显高于BPH组Trk A mRNA水平(t=8.097,P<0.0001),且Nedd4L mRNA水平与Trk A mRNA水平呈显著负相关(γ=-0.8029,P=0.0156)。2 Nedd4L水平与患者年龄、Gleason评分、TNM分期呈明显负相关(P<0.05),Trk A mRNA水平与患者年龄、Gleason评分、TNM分期呈显著正相关(P<0.05)。3PC组Trk A蛋白水平显著高于BPH组Trk A蛋白水平(t=11.06,P<0.0001),而PC组Trk A泛素化水平显著低于BPH组Trk A泛素化水平,差异具有统计学意义(t=5.538,P<0.0001)。结论前列腺癌患者中Nedd4L表达水平下调,Trk A表达水平上调,Trk A泛素化水平的降低与前列腺癌发生、发展及转移密切相关。

Objective To investigate the effect of Nedd4L on TrkA ubiquitination in patients with prostate cancer. Methods The levels of TrkA and Nedd4L in tissues of 60 patients with prostate cancer （ PC group） and 24 patients with benign prostatic hyperplasia （ BPH group ） were detected by fluorescence quantitative PCR and their correlation were analyzed. Meanwhile the relationship between TrkA and NedddL levels and clinical characteristics of prostate cancer （ age, Gleason score, TNM stage） were analyzed. TrkA protein level and TrkA ubiquitination level were tested by Western blot. Results ① The mRNA level of Nedd4L in PC group was significantly lower than that of BPH group （ t = 13.01 ,P 〈 0. 0001 ） ; while TrkA mRNA level in PC group was significantly higher than that of BPH group （ t = 8. 097, P 〈 0. 0001 ）. The Nedd4L mRNA level showed a significant negative correlation with TrkA mRNA level （ T = - 0. 8029, P = 0. 0156）. ②The level of Nedd4L displayed negative correlation with patient＇s age, Gleason score, and TNM stage （P 〈 0. 05 ） , while The level of TrkA showed a significant positive correlation with age, Gleason score and TNM stage （ P 〈 0.05 ）. ③The TrkA protein level in PC group was significantly higher than that of BPH group （ t = 11.06, P 〈 0. 0001 ）, while the level of TrkA ubiquitination was markedly lower than that of BPH group, there had statistically significant difference （t = 5. 538 ,P 〈 0. 0001 ）. Conclusion The level of Nedd4L decreased in prostate cancer and TrkA increased. Decreased level of TrkA ubiquitination is closely related to the development and transfer of prostate cancer.