LSD1与E-钙黏蛋白在胃癌中的表达及预后意义
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摘要
目的探讨赖氨酸特异性组蛋白去甲基化酶1(LSD1)和E-钙黏蛋白的表达与胃癌患者临床病理特征及对胃癌预后的意义。方法收集2012年1月至2013年12月该院收治的胃癌患者行手术切除的胃癌组织98例及健康胃组织76例。采用免疫组织化学技术检测手术标本中的LSD1、E-钙黏蛋白的表达情况,术后通过随访了解患者生存状况,随访截止2015年9月。分析两者与胃癌患者临床病理特征的关系、在胃癌组织中表达的相关性及对患者生存状况的影响。结果 LSD1的表达定位于细胞核,在胃癌细胞中的阳性表达率为63.3%,高于健康胃组织的45.9%,数据比较差异有统计学意义(P<0.05);E-钙黏蛋白定位于大多数腺细胞的细胞质膜,在胃癌细胞中E-钙黏蛋白的阳性表达率为63.2%显著低于健康胃组织80.3%,2组比较差异均有统计学意义(P<0.05);LSD1在不同的病理学分级的低、中、高分化的阳性表达率分别为81.6%、73.3%、40.0%,在TNM分期的Ⅰ~Ⅱ、Ⅲ~Ⅳ期中阳性表达率分别为56.6%、84.4%,在无和有淋巴结转移中分别为34.8%、73.3%,差异均有统计学意义(P<0.05);E-钙黏蛋白在不同的病理学分级的低、中、高分化的阳性表达率分别为52.6%、56.7%、80.0%;在TNM分期的Ⅰ~Ⅱ、Ⅲ~Ⅳ期中阳性表达率分别为62.3%、31.1%;在无和有淋巴结转移中分别为95.6%、52.0%,差异均有统计学意义(P<0.05),LSD1与E-钙黏蛋白在胃癌中的表达呈负相关(r=-0.335,P<0.05)。LSD1阳性表达的患者生存时间为(34.7±2.6)个月,2年总体生存率为34.8%,LSD1阴性表达的患者生存时间为(46.8±3.5)个月,2年总体生存率为60.2%,2组比较差异有统计学意义(P<0.05)。E-钙黏蛋白阳性表达的患者生存时间为(43.9±2.5)个月,2年总体生存率为45.3%,LSD1阴性表达的患者生存时间为(30.2±3.2)个月,2年总体生存率为28.5%,2组比较差异有统计学意义(P<0.05)。结论 LSD1在低分化胃癌、较晚TNM分期的胃癌组织中及有淋巴结转移的阳性表达率显著提高,而E-钙黏蛋白显著降低;2种蛋白的表达均为影响胃癌患者生存期的因素,且LSD1与E-低黏蛋白的表达呈负相关,阳性表达LSD1及阴性表达E-钙黏蛋白的胃癌患者预后较差。
Objective To study the relationship between expression of histone lysine specific demethylase 1(LSD1)and E-cadherin with clinicopathological features in the patients with gastric cancer and its prognosis significance.Methods Ninety-eight gastric tissue samples operatively resected from the patients with gastric cancer in our hospital from January 2012 to December 2013 and 76normal gastric tissue samples were collected.The immunohistochemical technology was used to detect the expression of LSD1 and E-cadherin in surgical specimens.The patients′survival situation was understood by postoperative follow-up.The followup was until September 2015.The relationship between LSD1 and E-cadherin with the clinicopathological features in the patients with gastric cancer,its relevance in gastric cancer expression and impact on survival situation of patients.Results The LSD1 expression was localized in the nucleus,the positive expression in gastric cancer cells was 63.3%,which was higher than 45.9%in normal gastric tissues,the difference was statistically significant(P<0.05);E-cadherin was present in the cytoplasmic membrane of most glandular cells,the positive expression rate of E-cadherin protein in gastric cancer cells was 63.2%,which was significantly lower than 80.3%in normal gastric tissues,the difference was statistically significant(P<0.05);the positive expression rates LSD1 in low,medium and high differentiations of different pathological grading were 81.6%,73.3%and 40.0%respectively;which in the TNM stageⅠ-Ⅱ and Ⅲ-Ⅳ were 56.6% and 84.4% respectively;which with and without lymph node metastasis were34.8% and 73.3% respectively,the differences were statistically significant(P<0.05);the positive expression rates of E-cadherin in low,medium and high differentiations of different pathological grading were 52.6%,56.7%and 80.0%respectively;which in the TNM stageⅠ-Ⅱ andⅢ-Ⅳ were 62.3% and 31.1% respectively;which with and without lymph node metastasis were 95.6%and 52.0% respectively,the differences were statistically significant(P<0.05);LSD1and E-cadherin expression in gastric cancer had a negative correlation(r=-0.335,P<0.05).The survival time in the patients with LSD1 positive expression was(34.7±2.6)months,and the 2-years overall survival rate was 34.8%,the survival time in the patients with LSD1 negative expression was(46.8±3.5)months,and the 2-years overall survival rate was 60.2%,the differences between the two groups were statistically significant(P<0.05);the survival time in the patients with E-cadherin positive expression was(43.9±2.5)months,and the 2-years overall survival was 45.3%,the survival time in the patients with LSD1 negative expression was(30.2±3.2)months,and the 2-years overall survival rate was 28.5%,the differences between the two groups were statistically significant(P<0.05).Conclusion The positive expression of LSD1 in poorly differentiated gastric cancer,gastric cancer tissue of late TNM stage and lymph node metastasis is significantly increased,while the E-cadherin is significantly decreased;the expression of the two proteins are the factors affecting the survival period in the patients with gastric cancer,moreover LSD1 is negatively correlated with E-cadherin expression,the gastric cancer patients with LSD1 positive expression and E-cadherin negative expression would have poorer prognosis.
Objective To study the relationship between expression of histone lysine specific demethylase 1(LSD1)and E-cadherin with clinicopathological features in the patients with gastric cancer and its prognosis significance.Methods Ninety-eight gastric tissue samples operatively resected from the patients with gastric cancer in our hospital from January 2012 to December 2013 and 76normal gastric tissue samples were collected.The immunohistochemical technology was used to detect the expression of LSD1 and E-cadherin in surgical specimens.The patients′survival situation was understood by postoperative follow-up.The followup was until September 2015.The relationship between LSD1 and E-cadherin with the clinicopathological features in the patients with gastric cancer,its relevance in gastric cancer expression and impact on survival situation of patients.Results The LSD1 expression was localized in the nucleus,the positive expression in gastric cancer cells was 63.3%,which was higher than 45.9%in normal gastric tissues,the difference was statistically significant(P<0.05);E-cadherin was present in the cytoplasmic membrane of most glandular cells,the positive expression rate of E-cadherin protein in gastric cancer cells was 63.2%,which was significantly lower than 80.3%in normal gastric tissues,the difference was statistically significant(P<0.05);the positive expression rates LSD1 in low,medium and high differentiations of different pathological grading were 81.6%,73.3%and 40.0%respectively;which in the TNM stageⅠ-Ⅱ and Ⅲ-Ⅳ were 56.6% and 84.4% respectively;which with and without lymph node metastasis were34.8% and 73.3% respectively,the differences were statistically significant(P<0.05);the positive expression rates of E-cadherin in low,medium and high differentiations of different pathological grading were 52.6%,56.7%and 80.0%respectively;which in the TNM stageⅠ-Ⅱ andⅢ-Ⅳ were 62.3% and 31.1% respectively;which with and without lymph node metastasis were 95.6%and 52.0% respectively,the differences were statistically significant(P<0.05);LSD1and E-cadherin expression in gastric cancer had a negative correlation(r=-0.335,P<0.05).The survival time in the patients with LSD1 positive expression was(34.7±2.6)months,and the 2-years overall survival rate was 34.8%,the survival time in the patients with LSD1 negative expression was(46.8±3.5)months,and the 2-years overall survival rate was 60.2%,the differences between the two groups were statistically significant(P<0.05);the survival time in the patients with E-cadherin positive expression was(43.9±2.5)months,and the 2-years overall survival was 45.3%,the survival time in the patients with LSD1 negative expression was(30.2±3.2)months,and the 2-years overall survival rate was 28.5%,the differences between the two groups were statistically significant(P<0.05).Conclusion The positive expression of LSD1 in poorly differentiated gastric cancer,gastric cancer tissue of late TNM stage and lymph node metastasis is significantly increased,while the E-cadherin is significantly decreased;the expression of the two proteins are the factors affecting the survival period in the patients with gastric cancer,moreover LSD1 is negatively correlated with E-cadherin expression,the gastric cancer patients with LSD1 positive expression and E-cadherin negative expression would have poorer prognosis.
引文
[1]邵根宝,黄晓佳,龚爱华,等.组蛋白去甲基化酶LSD1及其生物学功能[J].遗传,2010,32(4):331-338.
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[5]李蒙,吴玖斌,张培彤,等.E-钙黏蛋白、N-钙黏蛋白及波形蛋白在肿瘤转移中应用的研究进展[J].肿瘤研究与临床,2016,28(2):132-136.
[6]丁杰,廖国庆,张忠民,等.转录因子Slug、E-钙黏蛋白、N-钙黏蛋白在胃肠道间质瘤中的表达及其意义[J].中华医学杂志,2012,92(4):264-268.
[7]王金泗,陈晓耕,林孟波,等.Bcl-6共抑制因子样蛋白及E钙黏蛋白在胃癌中的表达及相关性分析[J].重庆医学,2014,43(20):2603-2605.
[8]赵媛,张连峰,刘蔚,等.原发性肝细胞癌组织中环氧化酶-2及E-钙黏蛋白的表达[J].郑州大学学报(医学版),2011,46(4):581-583.
[9]吴青松,李思荣,卢钦荣,等.胃癌根治术患者预后分析[J].广东医学,2012,33(23):3609-3611.
[10]杨学超,郝小康,王一理,等.HIF-1α、E-钙黏蛋白及p53在宫颈癌组织中的表达及临床意义[J].中国医学前沿杂志,2015,7(11):29-32.
[11]郑宝军,潘立峰,邵建富,等.细胞间黏附分子1和CD44V6及E钙黏蛋白在人胃癌组织中的表达及意义[J].中华胃肠外科杂志,2013,10(4):390-392.
[12]林树森,王锡山,邹德龄,等.E-钙黏蛋白在大肠癌中的表达及意义[J].哈尔滨医科大学学报,2011,43(6):576-579.
[13]阮建彬,臧建业.组蛋白去甲基化酶LSD1的结构和功能研究进展[J].中国科学技术大学学报,2012,38(8):930-940.
[2]荆璟,陈公琰.LSD1在恶性肿瘤中的研究进展[J].实用肿瘤学杂志,2014,17(6):569-572.
[3]沈琼,陈陆俊,徐斌,等.组蛋白赖氨酸去甲基化酶1在食管癌中的表达及其意义[J].中华实验外科杂志,2015,32(5):1168-1170.
[4]丁杰,张忠民,廖国庆,等.赖氨酸特异性去甲基化酶1在肿瘤领域的研究进展[J].医学与哲学,2015,23(2):57-60.
[5]李蒙,吴玖斌,张培彤,等.E-钙黏蛋白、N-钙黏蛋白及波形蛋白在肿瘤转移中应用的研究进展[J].肿瘤研究与临床,2016,28(2):132-136.
[6]丁杰,廖国庆,张忠民,等.转录因子Slug、E-钙黏蛋白、N-钙黏蛋白在胃肠道间质瘤中的表达及其意义[J].中华医学杂志,2012,92(4):264-268.
[7]王金泗,陈晓耕,林孟波,等.Bcl-6共抑制因子样蛋白及E钙黏蛋白在胃癌中的表达及相关性分析[J].重庆医学,2014,43(20):2603-2605.
[8]赵媛,张连峰,刘蔚,等.原发性肝细胞癌组织中环氧化酶-2及E-钙黏蛋白的表达[J].郑州大学学报(医学版),2011,46(4):581-583.
[9]吴青松,李思荣,卢钦荣,等.胃癌根治术患者预后分析[J].广东医学,2012,33(23):3609-3611.
[10]杨学超,郝小康,王一理,等.HIF-1α、E-钙黏蛋白及p53在宫颈癌组织中的表达及临床意义[J].中国医学前沿杂志,2015,7(11):29-32.
[11]郑宝军,潘立峰,邵建富,等.细胞间黏附分子1和CD44V6及E钙黏蛋白在人胃癌组织中的表达及意义[J].中华胃肠外科杂志,2013,10(4):390-392.
[12]林树森,王锡山,邹德龄,等.E-钙黏蛋白在大肠癌中的表达及意义[J].哈尔滨医科大学学报,2011,43(6):576-579.
[13]阮建彬,臧建业.组蛋白去甲基化酶LSD1的结构和功能研究进展[J].中国科学技术大学学报,2012,38(8):930-940.
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