自噬相关蛋白Beclin1、LC3-Ⅱ、Atg5在前列腺腺癌组织中的表达及意义
|
摘要
目的探讨自噬相关蛋白Beclin1、LC3-Ⅱ、Atg5在前列腺腺癌(PCa)中的表达情况及其临床意义。方法收集60例PCa标本(观察组)和15例良性前列腺增生(BPH)标本15例(对照组)。应用免疫组化法检测PCa组织和BPH组织中Beclin1、LC3-Ⅱ、Atg5的表达情况,比较两组间的差异;分析PCa组织中Beclin1、LC3-Ⅱ、Atg5蛋白的表达情况与PCa的Gleason评分、血清PSA水平、淋巴结转移、骨转移等临床参数之间的关系。结果 PCa组织中Beclin1、LC3-Ⅱ阳性表达率(38.3%、33.3%)明显低于BPH组织(60.0%、53.3%),而PCa组织中Atg5阳性表达率(83.3%)显著高于BPH组织(6.7%),差异均有统计学意义(均P<0.05)。Beclin1与LC3-Ⅱ的表达呈正相关,两者与Gleason评分、血清PSA水平、淋巴结转移、骨转移有关(均P<0.05),而与年龄无关(P>0.05)。Atg5的表达与年龄、Gleason评分、血清PSA水平、淋巴结转移、骨转移均无关(均P>0.05)。结论自噬相关蛋白Beclin1、LC3-Ⅱ、Atg5在PCa中的异常表达,提示自噬活动增强和自噬体形成增多在PCa发展过程中起着重要作用。
Objective To investigate the expression of Beclin1,LC3-Ⅱ and Atg5 in prostate adenocarcinoma(PCa) and its clinical significance.Methods The expression of Beclin1,LC3-Ⅱ and Atg5 was detected in 60 PCa tissue samples by immunohistochemical method,and the relationship between their expression levels and the clinical features of PCa patients was analyzed.Results The expressions of Beclin1 and LC3-Ⅱin PCa tissue was significantly lower and the expression Atg5 was significantly higher than those in benign prostate hyperplasia(BPH) tissue(P<0.05).There was a significant correlation between Belin1 and LC3-Ⅱ.The expression of Beclin1 and LC3-Ⅱwas associated with Gleason score,serum PSA level,lymph node metastasis and bone metastasis(P<0.05),but was not associated with age of patients(P >0.05);but no such association was observed for the expression of Atg5.Conclusion The abnormal expressions of autophagy-related proteins Beclin1,LC3-Ⅱ,Atg5 are observed in PCa,which may be involved in the occurrence and development of PCa.
Objective To investigate the expression of Beclin1,LC3-Ⅱ and Atg5 in prostate adenocarcinoma(PCa) and its clinical significance.Methods The expression of Beclin1,LC3-Ⅱ and Atg5 was detected in 60 PCa tissue samples by immunohistochemical method,and the relationship between their expression levels and the clinical features of PCa patients was analyzed.Results The expressions of Beclin1 and LC3-Ⅱin PCa tissue was significantly lower and the expression Atg5 was significantly higher than those in benign prostate hyperplasia(BPH) tissue(P<0.05).There was a significant correlation between Belin1 and LC3-Ⅱ.The expression of Beclin1 and LC3-Ⅱwas associated with Gleason score,serum PSA level,lymph node metastasis and bone metastasis(P<0.05),but was not associated with age of patients(P >0.05);but no such association was observed for the expression of Atg5.Conclusion The abnormal expressions of autophagy-related proteins Beclin1,LC3-Ⅱ,Atg5 are observed in PCa,which may be involved in the occurrence and development of PCa.
引文
[1]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[2]韩苏军,张思维,陈万青,等.中国前列腺癌发病现状和流行趋势分析[J].临床肿瘤学杂志,2014,18(4):330-334.
[3]张学昕,徐朝霞,赵海涛,等.MRI扩散加权成像诊断前列腺癌价值[J].中华实用诊断与治疗杂志,2014,28(5):502-503.
[4]韦艳,吴冰.细胞自噬与肿瘤[J].海南医学,2014,25(16):2413-2415.
[5]Liu C,Xu P,Chen D,et al.Roles of autophagy-related genes Belin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia[J].Biomed Rep,2013,1(6):855-860.
[6]贺慧杰,王功伟.前列腺癌Gleason评分重复性初步研究[J].中华男科学杂志,2016,22(1):37-41.
[7]刘成益,徐鹏程,陈德钢,等.自噬相关基因在前列腺癌及良性前列腺增生发生、发展中的作用[J].中华实验外科杂志,2013,30(11):2440.
[8]Ojha R,Bhattacharyya S,Singh SK.Autophagy in cancer stem cells:a potential link between chemoresistance,recurrence,and metastasis[J].Biores Open Access,2015,4(1):97-108.
[9]王贲士,陈德喜,郭洪亮.自噬与肿瘤的研究现状[J].中华肿瘤防治杂志,2014,21(8):637-640.
[10]Gewirtz DA.The four faces of autophagy:implication for cancer therapy[J].Cancer Res,2014,74(3):647-651.
[11]张甘霖,杨国旺,于明薇,等.自噬--中医药抗肿瘤研究的新方向[J].中华中医药杂志,2014(2):507-510.
[12]Wojcik S.Crosstalk between autophagy and proteasome protein degradation systems:possible implication for cancer therapy[J].Folia Histochem Cytobiol,2013,51(4):249-264.
[13]王文轩.前列腺癌与自噬的研究进展[J].国际泌尿系统杂志,2013,33(5):664-667.
[14]Liu C,Xu P,Chen D,et al.Roles of autophagy-related genes Beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia[J].Biomed Rep,2013,1(6):855-860.
[15]杨勇明,崔健,丁丽君,等.自噬相关蛋白Beclin1、MAPLC3在胃癌中的表达及临床意义[J].浙江医学,2013,35(23):2047-2049.
[16]Jiang P,Mizushima N.Autophagy and human disease[J].Cell Res,2014,24(1):69-79.
[17]Plantinga TS,van de Vosse E,Huijbers A,et al.Role of genetic variants of autophagy genes in susceptibility for non-medullary thyroid cancer and patients outcome[J].PloS One,2014,9(4):e94086.
[18]Tang JY,Fang YY,Hsi E,et al.Immunopositivity of Beclin-1 and ATG5 as indicators of survival and disease recurrence in oral squamous cell carcinoma[J].Anticancer Res,2013,33(12):5611-5616.
[19]张尊胜,梁军号,张铁龙,等.前列腺癌穿刺标本Gleason评分及穿刺阳性针数与术后病理切缘阳性之间的相关性分析[J].中国医师进修杂志,2014,37(11):12-14.
[20]Pezaro C,Woo HH,Davis ID.Prostate cancer:measuring PSA[J].Intern Med J,2014,44(5):433-440.
[21]张玉涛,王晓民,林相国,等.Beclin1、LC3在前列腺癌中表达及其与淋巴转移的关系[J].医学研究杂志,2016,45(7):96-99.
[22]刘成益,徐鹏程,陈德钢,等.Beclin-1、LC3与前列腺癌及良性前列腺增生的发生、发展及预防[J].国际泌尿系统杂志,2014,34(3):344-348.
[23]杜雄,李延新.Atg5与P504S在82例前列腺癌中的表达研究[J].肿瘤学杂志,2016,22(9):738-741.
[2]韩苏军,张思维,陈万青,等.中国前列腺癌发病现状和流行趋势分析[J].临床肿瘤学杂志,2014,18(4):330-334.
[3]张学昕,徐朝霞,赵海涛,等.MRI扩散加权成像诊断前列腺癌价值[J].中华实用诊断与治疗杂志,2014,28(5):502-503.
[4]韦艳,吴冰.细胞自噬与肿瘤[J].海南医学,2014,25(16):2413-2415.
[5]Liu C,Xu P,Chen D,et al.Roles of autophagy-related genes Belin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia[J].Biomed Rep,2013,1(6):855-860.
[6]贺慧杰,王功伟.前列腺癌Gleason评分重复性初步研究[J].中华男科学杂志,2016,22(1):37-41.
[7]刘成益,徐鹏程,陈德钢,等.自噬相关基因在前列腺癌及良性前列腺增生发生、发展中的作用[J].中华实验外科杂志,2013,30(11):2440.
[8]Ojha R,Bhattacharyya S,Singh SK.Autophagy in cancer stem cells:a potential link between chemoresistance,recurrence,and metastasis[J].Biores Open Access,2015,4(1):97-108.
[9]王贲士,陈德喜,郭洪亮.自噬与肿瘤的研究现状[J].中华肿瘤防治杂志,2014,21(8):637-640.
[10]Gewirtz DA.The four faces of autophagy:implication for cancer therapy[J].Cancer Res,2014,74(3):647-651.
[11]张甘霖,杨国旺,于明薇,等.自噬--中医药抗肿瘤研究的新方向[J].中华中医药杂志,2014(2):507-510.
[12]Wojcik S.Crosstalk between autophagy and proteasome protein degradation systems:possible implication for cancer therapy[J].Folia Histochem Cytobiol,2013,51(4):249-264.
[13]王文轩.前列腺癌与自噬的研究进展[J].国际泌尿系统杂志,2013,33(5):664-667.
[14]Liu C,Xu P,Chen D,et al.Roles of autophagy-related genes Beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia[J].Biomed Rep,2013,1(6):855-860.
[15]杨勇明,崔健,丁丽君,等.自噬相关蛋白Beclin1、MAPLC3在胃癌中的表达及临床意义[J].浙江医学,2013,35(23):2047-2049.
[16]Jiang P,Mizushima N.Autophagy and human disease[J].Cell Res,2014,24(1):69-79.
[17]Plantinga TS,van de Vosse E,Huijbers A,et al.Role of genetic variants of autophagy genes in susceptibility for non-medullary thyroid cancer and patients outcome[J].PloS One,2014,9(4):e94086.
[18]Tang JY,Fang YY,Hsi E,et al.Immunopositivity of Beclin-1 and ATG5 as indicators of survival and disease recurrence in oral squamous cell carcinoma[J].Anticancer Res,2013,33(12):5611-5616.
[19]张尊胜,梁军号,张铁龙,等.前列腺癌穿刺标本Gleason评分及穿刺阳性针数与术后病理切缘阳性之间的相关性分析[J].中国医师进修杂志,2014,37(11):12-14.
[20]Pezaro C,Woo HH,Davis ID.Prostate cancer:measuring PSA[J].Intern Med J,2014,44(5):433-440.
[21]张玉涛,王晓民,林相国,等.Beclin1、LC3在前列腺癌中表达及其与淋巴转移的关系[J].医学研究杂志,2016,45(7):96-99.
[22]刘成益,徐鹏程,陈德钢,等.Beclin-1、LC3与前列腺癌及良性前列腺增生的发生、发展及预防[J].国际泌尿系统杂志,2014,34(3):344-348.
[23]杜雄,李延新.Atg5与P504S在82例前列腺癌中的表达研究[J].肿瘤学杂志,2016,22(9):738-741.