假基因PTENP1在前列腺癌中的表达及与PSA水平的关系
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摘要
目的探讨10号染色体上磷酸酶与张力蛋白同源缺失性基因假基因1(PTENP1)在前列腺癌中的表达及与前列腺特异性抗原(PSA)的关系。方法收集2015年3月至2018年3月泌尿外科行手术切除的前列腺癌根治术或穿刺新鲜的前列腺癌患者64例为病例组,同时选择20例经组织病理学明确诊断为良性前列腺增生患者为对照组,再将64例前列腺癌患者按Gleason评分标准分成高、中、低分化组,检测前列腺癌组织中PTENP1、10号染色体上磷酸酶与张力蛋白同源缺失性基因(PTEN) mRNA的表达和血清中PSA的水平,并进行相关分析。结果与对照组相比,病例组PTENP1和PTEN mRNA的相对表达量降低,f/t PSA比值也降低,差异有统计学意义(P<0.05);血清tPSA和f-PSA水平增高,差异有统计学意义(P<0.05)。PTENP1和PTEN mRNA的相对表达量随着Gleason评分的增加而降低,f/t PSA比值也随着Gleason评分的增加而降低,差异有统计学意义(P<0.05);血清t-PSA和f-PSA水平随着Gleason评分的增加而增高,差异有统计学意义(P<0.05)。前列腺癌患者PTENP1 mRNA的相对表达量与PTEN mRNA的相对表达量、f/t PSA比值呈正相关(r=0.594、0.488,P<0.05);与Gleason评分、t-PSA和f-PSA呈负相关(r=-0.427、-0.720、-0.382,P<0.05)。结论 PTENP1在前列腺癌组织中表达显著下调,与Gleason评分和PSA呈负相关,因PTENP1不表达蛋白,提示其在mRNA水平对PTEN的表达具有调控作用。
Objective To investigate the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) pseudogene 1(PTENP1) on in prostate cancer and its relationship with prostate specific antigen(PSA).Methods A total of 64 patients with prostate cancer who underwent radical prostatectomy or biopsy of prostate gland in Department of Urology of our hospital from March 2015 to March 2018 were enrolled in case group.Twenty patients with benign prostatic hyperplasia who were diagnosed by histopathology were selected as the control group.All 64 patients with prostate cancer were divided into high,medium and low differentiation groups according to Gleason score.The expressions of PTEN mRNA and PTENP1,as well as the level of serum PSA,were detected in prostate cancer tissues for correlation analysis.Results As compared with those in control group,the relative expressions of PTENP1 and PTEN mRNA in the case group were decreased,and the f/t-PSA ratio was also decreased.The difference was statistically significant(P<0.05).However,serum t-PSA and fPSA levels were increased,an there was significant difference(P<0.05).The relative expressions of PTENP1 and PTEN mRNA as well as the f/t-PSA ratio were decreased with the increase of Gleason score,and the difference was statistically significant(P<0.05).The levels of serum t-PSA and f-PSA were increased with the increase of Gleason score,and significant differences were found(P<0.05).The relative expression of PTENP1 mRNA in prostate cancer patients was positively correlated with the relative expression of PTEN mRNA and the ratio of f/t-PSA(r=0.594,0.488,P<0.05),however,which was negatively correlated with Gleason score,t-PSA and f-PSA(r=-0.427,-0.720,-0.382,P<0.05).Conclusion The expression levels of PTENP1 are significantly down-regulated in prostate cancer tissues,which is negatively correlated with Gleason score and PSA.In addition,PTENP1 dose not express protein,which suggests that it can regulate the expression of PTEN at mRNA level.
Objective To investigate the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) pseudogene 1(PTENP1) on in prostate cancer and its relationship with prostate specific antigen(PSA).Methods A total of 64 patients with prostate cancer who underwent radical prostatectomy or biopsy of prostate gland in Department of Urology of our hospital from March 2015 to March 2018 were enrolled in case group.Twenty patients with benign prostatic hyperplasia who were diagnosed by histopathology were selected as the control group.All 64 patients with prostate cancer were divided into high,medium and low differentiation groups according to Gleason score.The expressions of PTEN mRNA and PTENP1,as well as the level of serum PSA,were detected in prostate cancer tissues for correlation analysis.Results As compared with those in control group,the relative expressions of PTENP1 and PTEN mRNA in the case group were decreased,and the f/t-PSA ratio was also decreased.The difference was statistically significant(P<0.05).However,serum t-PSA and fPSA levels were increased,an there was significant difference(P<0.05).The relative expressions of PTENP1 and PTEN mRNA as well as the f/t-PSA ratio were decreased with the increase of Gleason score,and the difference was statistically significant(P<0.05).The levels of serum t-PSA and f-PSA were increased with the increase of Gleason score,and significant differences were found(P<0.05).The relative expression of PTENP1 mRNA in prostate cancer patients was positively correlated with the relative expression of PTEN mRNA and the ratio of f/t-PSA(r=0.594,0.488,P<0.05),however,which was negatively correlated with Gleason score,t-PSA and f-PSA(r=-0.427,-0.720,-0.382,P<0.05).Conclusion The expression levels of PTENP1 are significantly down-regulated in prostate cancer tissues,which is negatively correlated with Gleason score and PSA.In addition,PTENP1 dose not express protein,which suggests that it can regulate the expression of PTEN at mRNA level.
引文
1 Malvezzi M,Bertuccio P,Rosso T,et al.European cancer mortality predictions for the year 2015:does lung cancer have the highest death rate in EU women.Annals of Oncology Official Journal of the European Society for Medical Oncology,2015,26:779-786.
2齐金蕾,王黎君,周脉耕,等.1990-2013年中国男性前列腺癌疾病负担分析.中华流行病学杂志,2016,37:778-782.
3朱晓东,郑安,王芝千,等.前列腺癌预防试验风险计算器在中国前列腺癌高危人群中的应用.中华男科学杂志,2018,24:142-146.
4戚庭月,李念芬,孙红光,等.经直肠超声造影检查在前列腺指示癌检测及大小评估中的应用价值.中华泌尿外科杂志,2016,37:766-771.
5 Uprimny C,Kroiss AS,Decristoforo C,et al.68 Ga-PSMA-11 PET/CT in primary staging of prostate cancer:PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.European Journal of Nuclear Medicine Molecular Imaging,2017,44:1-9.
6劳玲娟,宋新江,徐佳.PTEN在白藜芦醇对体外直肠癌细胞生长和凋亡的影响.中国中药杂志,2017,42:1730-1735.
7 Qian YY,Li K,Liu Q Y,et al.Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma.Oncotarget,2017,8:859-871.
8赵明,滕晓东,何向蕾,等.2014年国际泌尿病理协会前列腺癌分级系统新进展和新的预后分组.中华病理学杂志,2016,45:673-675.
9 Shi X,Nie F,Wang Z,et al.Pseudogene-expressed RNAs:a new frontier in cancers.Tumor Biology,2016,37:1471-1478.
10曹林平,吴健,郑树森.假基因在肿瘤中的研究.国际肿瘤学杂志,2014,41:11-13.
11 Masunaga A,Omatsu M,Kunimura T,et al.Expression of PTEN and its pseudogene PTENP1,and promoter methylation of PTEN in nontumourous thymus and thymic tumours.Journal of Clinical Pathology,2017,70:204-220.
12徐婷,王思雄,赖翔宇.替吉奥联合奥沙利铂对转移性三阴乳腺癌患者随机对照研究及对PTEN、p53的影响.基因组学与应用生物学,2016,35:3313-3318.
13洪艺华,刘曈彤,刘彦君,等.钒化合物通过活性氧水平的调节对PTEN表达缺失的前列腺癌细胞发挥更强的抑制作用.中国药学,2017,14:432-439.
14齐崇,晋强,王永恒,等.胶质母细胞瘤PTEN基因特异性表达的脑区分布研究.中华神经外科杂志,2016,32:158-161.
15 Wu YR,Qi HJ,Deng DF,et al.MicroRNA-21 promotes cell proliferation,migration,and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer.Tumour Biology the Journal of the International Society for Oncodevelopmental Biology Medicine,2016,37:1-10.
16余淦,欧正岳,陶启业,等.长链非编码RNA PTENP1在膀胱癌发生发展中的分子机制.南方医科大学学报,2017,37:1494-1500.
17 Wang L,Zhang N,Wang Z,et al.Pseudogene PTENP1 functions as a competing endogenous RNA(ceRNA)to regulate PTEN expression by sponging miR-499-5p.Biochemistry,2016,81:739-747.
18夏加增,过小强,邓凯元,等.假基因PTENP1通过调控PTEN蛋白的表达影响胃癌进展的研究.临床与病理杂志,2015,35:73.
19 Poliseno L,Salmena L,Zhang J,et al.A coding-independent function of gene and pseudogene mRNAs regulates tumour biology.Nature,2015,465:1033-1038.
20祁新坤,舒逸,秦茹,等.EB病毒和人巨细胞病毒感染对儿童急性淋巴细胞白血病PTEN及hTERT基因甲基化的影响.南方医科大学学报,2017,37:1678-1681.
2齐金蕾,王黎君,周脉耕,等.1990-2013年中国男性前列腺癌疾病负担分析.中华流行病学杂志,2016,37:778-782.
3朱晓东,郑安,王芝千,等.前列腺癌预防试验风险计算器在中国前列腺癌高危人群中的应用.中华男科学杂志,2018,24:142-146.
4戚庭月,李念芬,孙红光,等.经直肠超声造影检查在前列腺指示癌检测及大小评估中的应用价值.中华泌尿外科杂志,2016,37:766-771.
5 Uprimny C,Kroiss AS,Decristoforo C,et al.68 Ga-PSMA-11 PET/CT in primary staging of prostate cancer:PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.European Journal of Nuclear Medicine Molecular Imaging,2017,44:1-9.
6劳玲娟,宋新江,徐佳.PTEN在白藜芦醇对体外直肠癌细胞生长和凋亡的影响.中国中药杂志,2017,42:1730-1735.
7 Qian YY,Li K,Liu Q Y,et al.Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma.Oncotarget,2017,8:859-871.
8赵明,滕晓东,何向蕾,等.2014年国际泌尿病理协会前列腺癌分级系统新进展和新的预后分组.中华病理学杂志,2016,45:673-675.
9 Shi X,Nie F,Wang Z,et al.Pseudogene-expressed RNAs:a new frontier in cancers.Tumor Biology,2016,37:1471-1478.
10曹林平,吴健,郑树森.假基因在肿瘤中的研究.国际肿瘤学杂志,2014,41:11-13.
11 Masunaga A,Omatsu M,Kunimura T,et al.Expression of PTEN and its pseudogene PTENP1,and promoter methylation of PTEN in nontumourous thymus and thymic tumours.Journal of Clinical Pathology,2017,70:204-220.
12徐婷,王思雄,赖翔宇.替吉奥联合奥沙利铂对转移性三阴乳腺癌患者随机对照研究及对PTEN、p53的影响.基因组学与应用生物学,2016,35:3313-3318.
13洪艺华,刘曈彤,刘彦君,等.钒化合物通过活性氧水平的调节对PTEN表达缺失的前列腺癌细胞发挥更强的抑制作用.中国药学,2017,14:432-439.
14齐崇,晋强,王永恒,等.胶质母细胞瘤PTEN基因特异性表达的脑区分布研究.中华神经外科杂志,2016,32:158-161.
15 Wu YR,Qi HJ,Deng DF,et al.MicroRNA-21 promotes cell proliferation,migration,and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer.Tumour Biology the Journal of the International Society for Oncodevelopmental Biology Medicine,2016,37:1-10.
16余淦,欧正岳,陶启业,等.长链非编码RNA PTENP1在膀胱癌发生发展中的分子机制.南方医科大学学报,2017,37:1494-1500.
17 Wang L,Zhang N,Wang Z,et al.Pseudogene PTENP1 functions as a competing endogenous RNA(ceRNA)to regulate PTEN expression by sponging miR-499-5p.Biochemistry,2016,81:739-747.
18夏加增,过小强,邓凯元,等.假基因PTENP1通过调控PTEN蛋白的表达影响胃癌进展的研究.临床与病理杂志,2015,35:73.
19 Poliseno L,Salmena L,Zhang J,et al.A coding-independent function of gene and pseudogene mRNAs regulates tumour biology.Nature,2015,465:1033-1038.
20祁新坤,舒逸,秦茹,等.EB病毒和人巨细胞病毒感染对儿童急性淋巴细胞白血病PTEN及hTERT基因甲基化的影响.南方医科大学学报,2017,37:1678-1681.
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