自噬相关蛋白在肾透明细胞癌与癌旁组织中表达状况对比
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摘要
目的:对比自噬相关蛋白在肾透明细胞癌与癌旁组织中表达状况。方法:选取2016年3月20日-2017年3月20日本院收治的50例实施根治性肾切除术患者为研究对象,手术过程中切取患者两部分组织,一部分为癌变组织,一部分为癌旁组织(即正常组织),且将其制作为标本,对其进行免疫组化染色测定、组织芯片制作、IMAGE PRO PLUS6.0软件测量,并对自噬相关蛋白表达水平变化进行相关性分析。结果:从免疫组化染色评分角度分析,肿瘤组织的ATG7(1.36±0.58)、LC3(2.05±0.36)、Beclin 1(0.55±0.32)水平均低于正常组织[(2.63±0.78)、(3.48±0.45)、(2.47±0.69)],而ULK1(3.69±0.45)、P62(3.54±0.37)、P-m TOR(2.99±0.85)均高于正常组织[(2.69±0.35)、(2.31±0.45)、(2.05±0.36)],差异均有统计学意义(P<0.05),肿瘤组织和正常组织的ATG5值分别为(2.67±0.54)、(2.45±0.66),差异无统计学意义(P>0.05);从IMAGE PRO PLUS6.0软件测量结果角度分析,肿瘤组织的ATG7(0.029±0.010)、LC3(0.021±0.010)、Beclin 1(0.003±0.006)、P-m TOR(0.038±0.019)均低于正常组织[(0.034±0.020)、(0.043±0.015)、(0.023±0.016)、(0.031±0.013)],而P62(0.029±0.018)、ULK1(0.032±0.014)均高于正常组织(0.020±0.009、0.025±0.010),差异均有统计学意义(P<0.05),肿瘤组织和正常组织的ATG5值分别为(0.034±0.020)、(0.043±0.010),差异无统计学意义(P>0.05);根据自噬相关蛋白表达水平变化的相关性分析结果,P-m TOR、LC3、P62的表达与ATG7的表达水平变化有关,Beclin 1的表达与其他蛋白不相关,ULK1的表达变化与ATG7和P62相关。结论:自噬的表达水平在肾透明细胞癌中表现为下调状态,而其下调可受到ATG7、LC3、Beclin 1、ULK1、P62、P-m TOR等多种自噬相关蛋白协同影响。
Objective:To explore the expression of autophagy related protein in renal cell carcinoma and adjacent tissues.Method:From March 2016 to March 2017,50 cases with radical nephrectomy were selected as the experimental object.During the operation,part of cancerous tissue and adjacent tissues(normal tissue) of patients were cut out to make specimens which were processed by immunohistochemical staining,made to tissue microarray and measured by IMAGE PRO PLUS6.0 software.Correlation analysis of autophagy related protein expression were conducted.Result:According to the immunohistochemical staining score,ATG7(1.36±0.58),LC3(2.05±0.36),Beclin 1(0.55±0.32) of cancerous tissue were lower than ATG7(2.63±0.78),LC3(3.48±0.45),Beclin 1(2.47±0.69) of adjacent tissues,ULK1(3.69±0.45),P62(3.54±0.37),P-m TOR(2.99±0.85) of cancerous tissue were higher than ULK1(2.69±0.35),P62(2.31±0.45),P-m TOR(2.05±0.36) of adjacent tissues,the differences had statistical significance(P<0.05),ATG5 of tumor tissues and normal tissues were(2.67±0.54),(2.45±0.66),the difference had no statistical significance(P>0.05).By the measurement results of IMAGE PRO PLUS6.0 software,ATG7(0.029±0.010),LC3(0.021±0.010),Beclin 1(0.003±0.006),P-m TOR(0.038±0.019) of cancerous tissue were lower than ATG7(0.034±0.020),LC3(0.043±0.015),Beclin 1(0.023±0.016),P-m TOR(0.031±0.013) of adjacent tissues,and P62(0.029±0.018),ULK1(0.032±0.014) of cancerous tissue were higher than P62(0.020±0.009),ULK1(0.025±0.010) of adjacent tissues,the differences had statistical significance(P<0.05),ATG5 of tumor tissue and normal tissue were(0.034±0.020),(0.043±0.010),the difference had no statistical significance(P>0.05).From the perspective of correlation analysis,the expression of P-m TOR,LC3,P62 was related to the expression level of ATG7.The expression of Beclin 1 was not related to other proteins.The expression of ULK1 was correlated with ATG7 and P62.Conclusion:The expression level of autophagy is down regulated in renal clear cell carcinoma,and its down-regulation may be affected by ATG7,LC3,Beclin 1,ULK1,P62,P-m TOR and other autophagy related proteins.
Objective:To explore the expression of autophagy related protein in renal cell carcinoma and adjacent tissues.Method:From March 2016 to March 2017,50 cases with radical nephrectomy were selected as the experimental object.During the operation,part of cancerous tissue and adjacent tissues(normal tissue) of patients were cut out to make specimens which were processed by immunohistochemical staining,made to tissue microarray and measured by IMAGE PRO PLUS6.0 software.Correlation analysis of autophagy related protein expression were conducted.Result:According to the immunohistochemical staining score,ATG7(1.36±0.58),LC3(2.05±0.36),Beclin 1(0.55±0.32) of cancerous tissue were lower than ATG7(2.63±0.78),LC3(3.48±0.45),Beclin 1(2.47±0.69) of adjacent tissues,ULK1(3.69±0.45),P62(3.54±0.37),P-m TOR(2.99±0.85) of cancerous tissue were higher than ULK1(2.69±0.35),P62(2.31±0.45),P-m TOR(2.05±0.36) of adjacent tissues,the differences had statistical significance(P<0.05),ATG5 of tumor tissues and normal tissues were(2.67±0.54),(2.45±0.66),the difference had no statistical significance(P>0.05).By the measurement results of IMAGE PRO PLUS6.0 software,ATG7(0.029±0.010),LC3(0.021±0.010),Beclin 1(0.003±0.006),P-m TOR(0.038±0.019) of cancerous tissue were lower than ATG7(0.034±0.020),LC3(0.043±0.015),Beclin 1(0.023±0.016),P-m TOR(0.031±0.013) of adjacent tissues,and P62(0.029±0.018),ULK1(0.032±0.014) of cancerous tissue were higher than P62(0.020±0.009),ULK1(0.025±0.010) of adjacent tissues,the differences had statistical significance(P<0.05),ATG5 of tumor tissue and normal tissue were(0.034±0.020),(0.043±0.010),the difference had no statistical significance(P>0.05).From the perspective of correlation analysis,the expression of P-m TOR,LC3,P62 was related to the expression level of ATG7.The expression of Beclin 1 was not related to other proteins.The expression of ULK1 was correlated with ATG7 and P62.Conclusion:The expression level of autophagy is down regulated in renal clear cell carcinoma,and its down-regulation may be affected by ATG7,LC3,Beclin 1,ULK1,P62,P-m TOR and other autophagy related proteins.
引文
[1]朱少群,钟美花.磁共振成像技术在18例臂丛神经损伤诊断中的应用[J].中国民族民间医药,2016,25(4):115,117.
[2]唐怡.ART1调节饥饿诱导的结肠癌细胞自噬及其对癌细胞增殖凋亡影响的研究[D].重庆:重庆医科大学,2015.
[3]宋孟锜,薛寅凯,孙运秀,等.自噬相关哺乳动物雷帕霉素靶蛋白、微管相关蛋白1轻链3-β在肝细胞癌组织中的表达及其临床意义[J].中华实验外科杂志,2014,31(5):1108-1110.
[4]吴楠,闵鹤鸣,屈惠莹,等.自噬基因p ULK、PI3KC3在非小细胞肺癌中的表达及相关性研究[J].天津医药,2015,56(6):635-638,706.
[5]赵亚通,刘超,庞志刚,等.叉头转录因子O亚家族1及自噬相关蛋白微管相关蛋白1轻链3-Ⅱ在肝癌组织的表达及意义[J].中华实验外科杂志,2016,33(2):492-494.
[6]沈芸,向阳,肖长纪,等.转录因子c-Jun对甲氨蝶呤耐药绒毛膜癌细胞内自噬标志蛋白LC3的调节作用[J].中华妇产科杂志,2014,8(7):531-535.
[7]郭凯,黄波,王晓东,等.自噬相关蛋白在肺鳞癌和腺癌组织中的表达及相关性研究[J].天津医药,2014,74(6):536-539.
[8]邵乐宁,杨晓东,邢春根,等.肿瘤相关巨噬细胞自噬状态对人大肠癌细胞凋亡的影响[J].中华实验外科杂志,2014,31(7):1504-1507.
[9]陈佳,王琪,张玮,等.下调MTRR基因表达对顺铂耐药的卵巢上皮性癌细胞自噬和凋亡的影响及机制研究[J].中华妇产科杂志,2016,51(4):285-292.
[10]刘永青.自噬在天然小分子化合物促进前列腺癌细胞死亡中的作用及其机制研究[D].济南:山东大学,2015.
[11]许赤,蔡惠宁,李翠平,等.RNA干扰技术下调营养缺乏自噬因子1表达对肝癌细胞侵袭转移能力的影响[J].中华细胞与干细胞杂志(电子版),2016,6(2):80-85.
[12]斯庆图娜拉.联合自噬抑制剂增加PI3K/m TOR抑制剂NVPBEZ235诱导的结肠癌细胞凋亡[J].中国实验诊断学,2015,85(10):1632-1635.
[13]薛妮娜.新型HSP90抑制剂筛选及抗胰腺癌增殖作用和分子机制研究;SHP90抑制剂诱导胰腺癌细胞IGF-1Rβ自噬性降解的分子机制研究[D].北京:北京协和医学院中国医学科学院,2015.
[14]宋建,梁素美,高俊,等.自噬基因LC3B在肺鳞癌中的表达意义及与窖蛋白-1的关系[J].中华临床医师杂志(电子版),2013,78(22):10 029-10 034.
[15]马泰.细胞自噬在肝癌细胞内质网应激性死亡中的作用及对药物敏感性的影响[D].合肥:安徽医科大学,2013.
[16]冯仰伟.自噬相关基因Beclin-1、LC3和增殖细胞核抗原Ki-67在子宫内膜腺癌组织中的表达及意义[D].泰山:泰山医学院,2015.
[17]张泽兵,全海英,张桐菲,等.自噬在Tca83细胞中的作用及自噬相关基因的表达[J].中华口腔医学杂志,2012,47(z1):233-238.
[18]朱兴春,刘青松,杨慧敏,等.末端结合蛋白1(EB1)在宫颈组织中的表达及其对自噬标志蛋白表达的影响[J].复旦学报(医学版),2014,41(5):641-646.
[19]范大为,刘凯,袁成刚,等.Beclin-1与EZH2在肾透明细胞癌中的表达及其意义[J].新医学,2016,47(5):329-334.
[20]倪晓辰,赵志红,马永良,等.桧木醇诱导人肾透明细胞癌786-O细胞凋亡及其机制研究[J].中国肿瘤临床,2015,45(1):43-46.
[21]张琦,Shuhui Si,Sue Schoen,等.自噬对Folliculin基因缺陷的肾癌细胞放疗敏感性的影响[J].泌尿外科杂志(电子版),2015,52(3):16-22,54.
[2]唐怡.ART1调节饥饿诱导的结肠癌细胞自噬及其对癌细胞增殖凋亡影响的研究[D].重庆:重庆医科大学,2015.
[3]宋孟锜,薛寅凯,孙运秀,等.自噬相关哺乳动物雷帕霉素靶蛋白、微管相关蛋白1轻链3-β在肝细胞癌组织中的表达及其临床意义[J].中华实验外科杂志,2014,31(5):1108-1110.
[4]吴楠,闵鹤鸣,屈惠莹,等.自噬基因p ULK、PI3KC3在非小细胞肺癌中的表达及相关性研究[J].天津医药,2015,56(6):635-638,706.
[5]赵亚通,刘超,庞志刚,等.叉头转录因子O亚家族1及自噬相关蛋白微管相关蛋白1轻链3-Ⅱ在肝癌组织的表达及意义[J].中华实验外科杂志,2016,33(2):492-494.
[6]沈芸,向阳,肖长纪,等.转录因子c-Jun对甲氨蝶呤耐药绒毛膜癌细胞内自噬标志蛋白LC3的调节作用[J].中华妇产科杂志,2014,8(7):531-535.
[7]郭凯,黄波,王晓东,等.自噬相关蛋白在肺鳞癌和腺癌组织中的表达及相关性研究[J].天津医药,2014,74(6):536-539.
[8]邵乐宁,杨晓东,邢春根,等.肿瘤相关巨噬细胞自噬状态对人大肠癌细胞凋亡的影响[J].中华实验外科杂志,2014,31(7):1504-1507.
[9]陈佳,王琪,张玮,等.下调MTRR基因表达对顺铂耐药的卵巢上皮性癌细胞自噬和凋亡的影响及机制研究[J].中华妇产科杂志,2016,51(4):285-292.
[10]刘永青.自噬在天然小分子化合物促进前列腺癌细胞死亡中的作用及其机制研究[D].济南:山东大学,2015.
[11]许赤,蔡惠宁,李翠平,等.RNA干扰技术下调营养缺乏自噬因子1表达对肝癌细胞侵袭转移能力的影响[J].中华细胞与干细胞杂志(电子版),2016,6(2):80-85.
[12]斯庆图娜拉.联合自噬抑制剂增加PI3K/m TOR抑制剂NVPBEZ235诱导的结肠癌细胞凋亡[J].中国实验诊断学,2015,85(10):1632-1635.
[13]薛妮娜.新型HSP90抑制剂筛选及抗胰腺癌增殖作用和分子机制研究;SHP90抑制剂诱导胰腺癌细胞IGF-1Rβ自噬性降解的分子机制研究[D].北京:北京协和医学院中国医学科学院,2015.
[14]宋建,梁素美,高俊,等.自噬基因LC3B在肺鳞癌中的表达意义及与窖蛋白-1的关系[J].中华临床医师杂志(电子版),2013,78(22):10 029-10 034.
[15]马泰.细胞自噬在肝癌细胞内质网应激性死亡中的作用及对药物敏感性的影响[D].合肥:安徽医科大学,2013.
[16]冯仰伟.自噬相关基因Beclin-1、LC3和增殖细胞核抗原Ki-67在子宫内膜腺癌组织中的表达及意义[D].泰山:泰山医学院,2015.
[17]张泽兵,全海英,张桐菲,等.自噬在Tca83细胞中的作用及自噬相关基因的表达[J].中华口腔医学杂志,2012,47(z1):233-238.
[18]朱兴春,刘青松,杨慧敏,等.末端结合蛋白1(EB1)在宫颈组织中的表达及其对自噬标志蛋白表达的影响[J].复旦学报(医学版),2014,41(5):641-646.
[19]范大为,刘凯,袁成刚,等.Beclin-1与EZH2在肾透明细胞癌中的表达及其意义[J].新医学,2016,47(5):329-334.
[20]倪晓辰,赵志红,马永良,等.桧木醇诱导人肾透明细胞癌786-O细胞凋亡及其机制研究[J].中国肿瘤临床,2015,45(1):43-46.
[21]张琦,Shuhui Si,Sue Schoen,等.自噬对Folliculin基因缺陷的肾癌细胞放疗敏感性的影响[J].泌尿外科杂志(电子版),2015,52(3):16-22,54.