乳腺癌中Ulk1过表达与患者TNM分期和癌症复发的关系研究
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摘要
目的:探讨乳腺癌中Ulk1过表达与患者TNM分期和癌症复发的关系。方法:选取2013年3月—2015年5月在本院治疗的乳腺癌患者196例,根据TMN分期分为T1期94例、T2期42例、T3期36例、T4期24例,检测并观察不同分期患者的Ulk1蛋白表达及阳性率,分析Ulk1蛋白表达与临床病理特征的关系、乳腺癌患者癌症复发因素。结果:T1期Ulk1蛋白表达均高于T2、T3、T4期,T2期Ulk1蛋白表达均高于T3、T4期,T3期Ulk1蛋白表达高于T4期,差异均有统计学意义(P<0.05);T1、T2、T3、T4期患者Ulk1阳性率逐渐降低(P<0.05);Ulk1蛋白表达与年龄无关(P>0.05),分化程度越高、浸润深度越深、有淋巴血管间隙浸润、有淋巴结转移,Ulk1蛋白阳性表达率越低(P<0.05);有淋巴结转移、有淋巴血管间隙浸润是乳腺癌患者癌症复发的危险因素(OR=4.20、5.02,P<0.05),Ulk1蛋白表达阳性是乳腺癌患者癌症复发的保护因素(OR=0.48,P<0.05)。结论:Ulk1蛋白在乳腺癌的发生进展过程中起抑制作用,TNM分期越高,Ulk1蛋白阳性率越低,Ulk1蛋白表达阳性是乳腺癌患者癌症复发的保护因素。
Objective:To investigate the relationship between Ulk1 overexpression in breast cancer and TNM staging and cancer recurrence.Method:A total of 196 patients with breast cancer in our hospital from March 2013 to May 2015 were selected.According to TMN stage,they were divided into 94 patients with T1 stage,42 patients with T2 stage,36 patients with T3 stage and 24 patients with T4 stage.The expression and positive rate of Ulk1 protein in patients with different stages were detected and observed,the relationship between Ulk1 protein expression and clinicopathological characteristics and the recurrence factors of breast cancer were analyzed.Result:The expression of Ulk1 protein in stage T1 was higher than those of stage T2,T3 and T4,the expression of Ulk1 protein in stage T2 was higher than those of stage T3 and T4,and the expression of Ulk1 protein in stage T3 was higher than that of stage T4,the differences were statistically significant(P<0.05).The positive rate of Ulk1 in patients with stage T1,T2,T3 and T4 decreased gradually(P<0.05).The expression of Ulk1 protein was not related to age(P>0.05),the higher the differentiation degree,the deeper the infiltration depth,the infiltration of lymphatic vessel space and lymph node metastasis,the lower the positive expression rate of Ulk1 protein(P<0.05).Lymph node metastasis and lymphatic interstitial infiltration were risk factors for cancer recurrence in breast cancer patients(OR=4.20,5.02,P<0.05),positive expression of Ulk1 protein was a protective factor for cancer recurrence in breast cancer patients(OR=0.48,P<0.05).Conclusion:Ulk1 protein inhibits the occurrence and progression of breast cancer,the higher TNM stage,the lower the positive rate of Ulk1 protein,the positive expression of Ulk1 protein is a protective factor for cancer recurrence in breast cancer patients.
Objective:To investigate the relationship between Ulk1 overexpression in breast cancer and TNM staging and cancer recurrence.Method:A total of 196 patients with breast cancer in our hospital from March 2013 to May 2015 were selected.According to TMN stage,they were divided into 94 patients with T1 stage,42 patients with T2 stage,36 patients with T3 stage and 24 patients with T4 stage.The expression and positive rate of Ulk1 protein in patients with different stages were detected and observed,the relationship between Ulk1 protein expression and clinicopathological characteristics and the recurrence factors of breast cancer were analyzed.Result:The expression of Ulk1 protein in stage T1 was higher than those of stage T2,T3 and T4,the expression of Ulk1 protein in stage T2 was higher than those of stage T3 and T4,and the expression of Ulk1 protein in stage T3 was higher than that of stage T4,the differences were statistically significant(P<0.05).The positive rate of Ulk1 in patients with stage T1,T2,T3 and T4 decreased gradually(P<0.05).The expression of Ulk1 protein was not related to age(P>0.05),the higher the differentiation degree,the deeper the infiltration depth,the infiltration of lymphatic vessel space and lymph node metastasis,the lower the positive expression rate of Ulk1 protein(P<0.05).Lymph node metastasis and lymphatic interstitial infiltration were risk factors for cancer recurrence in breast cancer patients(OR=4.20,5.02,P<0.05),positive expression of Ulk1 protein was a protective factor for cancer recurrence in breast cancer patients(OR=0.48,P<0.05).Conclusion:Ulk1 protein inhibits the occurrence and progression of breast cancer,the higher TNM stage,the lower the positive rate of Ulk1 protein,the positive expression of Ulk1 protein is a protective factor for cancer recurrence in breast cancer patients.
引文
[1]左婷婷,陈万青.中国乳腺癌全人群生存率分析研究进展[J].中国肿瘤临床,2016,43(14):639-642.
[2]杨玲,李连弟,陈育德,等.中国乳腺癌发病死亡趋势的估计与预测[J].中华肿瘤杂志,2006,28(6):438-440.
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[5]王乐,张玥,石菊芳,等.中国女性乳腺癌疾病负担分析[J].中华流行病学杂志,2016,37(7):970-976.
[6]李肃,孙海明,孙冬琳,等.AMPK-mTOR-ULK1/2信号通路与自噬[J].国际遗传学杂志,2017,40(1):39-44.
[7]任国文,陆金健,陈修平.补骨脂定通过活性氧诱导乳腺癌MCF-7细胞DNA损伤和自噬[J].中国药理学通报,2015,31(S1):237.
[8]汤建中,张涛,丁淑琴,等.pSicoR/miR-17-5p靶向调控UNC-51样激酶1(ULK1)及其对细胞自噬的影响[J/OL].临床检验杂志(电子版),2014,3(3):698-704.
[9]纪小志,张仁敏,仲悦娇,等.ULK1在胃癌中的表达及其临床意义[J].临床肿瘤学杂志,2017,22(12):1103-1106.
[10]Kim J H,Seo D,Kim S J,et al.The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation[J].EMBO Rep,2018,19(4):e44378.
[11]吴银霞,周广臣,牛荃,等.自噬相关基因ULK1在前列腺癌中的表达及临床意义[J].现代泌尿外科杂志,2017,22(9):666-668.
[12]康伊,张艳,张伟.转化生长因子β信号在内皮细胞中通过上调ULK1蛋白抑制细胞周期[J].中国医科大学学报,2018,47(9):783-787.
[13]江山,黎博一,张涛,等.自噬相关基因ULK1在外阴鳞癌中的表达及临床意义[J].解放军医学杂志,2016,41(3):211-215.
[14]詹义凤,薛敬玲,汤泉泉,等.ULK1、p53在大肠癌及癌前病变中的表达及临床意义[J].数理医药学杂志,2018,31(10):1430-1432.
[15]杨龙灿,张莹,余曦,等.细胞自噬与ULK1蛋白关系的研究进展[J].医学综述,2018,24(23):4635-4639,4646.
[16]卢岩岩,姚楠,许学猛,等.miRNA-140靶向结合自噬相关基因ULK1的验证[J].中国组织工程研究,2018,22(24):3831-3836.
[17]刘欣韵,蒋小芹,鲍晶晶,等.UNC-51样激酶1在食管癌组织中的表达及其意义[J].江苏大学学报(医学版),2018,28(6):521-524.
[18]吴淑华,何双,胡金龙,等.RNA干扰靶向抑制自噬调控基因Beclin 1对结肠癌细胞株HCT116自噬活性及增殖/凋亡的影响[J].临床与实验病理学杂志,2014,30(6):599-604.
[19]闫兵,任雅丽,何群,等.自噬相关蛋白在肾透明细胞癌与癌旁组织中表达状况的比较研究[J].中华泌尿外科杂志,2013,34(11):823-826.
[20]赵敏,张瑜,张岚,等.丹酚酸B通过mTOR/Ulk1信号通路诱导胶质瘤细胞C6自噬性死亡[J].中国免疫学杂志,2018,34(4):549-552.
[2]杨玲,李连弟,陈育德,等.中国乳腺癌发病死亡趋势的估计与预测[J].中华肿瘤杂志,2006,28(6):438-440.
[3]徐兵河,江泽飞,胡夕春.中国晚期乳腺癌临床诊疗专家共识2016[J].中华医学杂志,2016,96(22):1719-1727.
[4]郑莹,吴春晓,张敏璐.乳腺癌在中国的流行状况和疾病特征[J].中国癌症杂志,2013,23(8):561-569.
[5]王乐,张玥,石菊芳,等.中国女性乳腺癌疾病负担分析[J].中华流行病学杂志,2016,37(7):970-976.
[6]李肃,孙海明,孙冬琳,等.AMPK-mTOR-ULK1/2信号通路与自噬[J].国际遗传学杂志,2017,40(1):39-44.
[7]任国文,陆金健,陈修平.补骨脂定通过活性氧诱导乳腺癌MCF-7细胞DNA损伤和自噬[J].中国药理学通报,2015,31(S1):237.
[8]汤建中,张涛,丁淑琴,等.pSicoR/miR-17-5p靶向调控UNC-51样激酶1(ULK1)及其对细胞自噬的影响[J/OL].临床检验杂志(电子版),2014,3(3):698-704.
[9]纪小志,张仁敏,仲悦娇,等.ULK1在胃癌中的表达及其临床意义[J].临床肿瘤学杂志,2017,22(12):1103-1106.
[10]Kim J H,Seo D,Kim S J,et al.The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation[J].EMBO Rep,2018,19(4):e44378.
[11]吴银霞,周广臣,牛荃,等.自噬相关基因ULK1在前列腺癌中的表达及临床意义[J].现代泌尿外科杂志,2017,22(9):666-668.
[12]康伊,张艳,张伟.转化生长因子β信号在内皮细胞中通过上调ULK1蛋白抑制细胞周期[J].中国医科大学学报,2018,47(9):783-787.
[13]江山,黎博一,张涛,等.自噬相关基因ULK1在外阴鳞癌中的表达及临床意义[J].解放军医学杂志,2016,41(3):211-215.
[14]詹义凤,薛敬玲,汤泉泉,等.ULK1、p53在大肠癌及癌前病变中的表达及临床意义[J].数理医药学杂志,2018,31(10):1430-1432.
[15]杨龙灿,张莹,余曦,等.细胞自噬与ULK1蛋白关系的研究进展[J].医学综述,2018,24(23):4635-4639,4646.
[16]卢岩岩,姚楠,许学猛,等.miRNA-140靶向结合自噬相关基因ULK1的验证[J].中国组织工程研究,2018,22(24):3831-3836.
[17]刘欣韵,蒋小芹,鲍晶晶,等.UNC-51样激酶1在食管癌组织中的表达及其意义[J].江苏大学学报(医学版),2018,28(6):521-524.
[18]吴淑华,何双,胡金龙,等.RNA干扰靶向抑制自噬调控基因Beclin 1对结肠癌细胞株HCT116自噬活性及增殖/凋亡的影响[J].临床与实验病理学杂志,2014,30(6):599-604.
[19]闫兵,任雅丽,何群,等.自噬相关蛋白在肾透明细胞癌与癌旁组织中表达状况的比较研究[J].中华泌尿外科杂志,2013,34(11):823-826.
[20]赵敏,张瑜,张岚,等.丹酚酸B通过mTOR/Ulk1信号通路诱导胶质瘤细胞C6自噬性死亡[J].中国免疫学杂志,2018,34(4):549-552.