赖氨酸特异性去甲基化酶1在胃癌组织中的表达及意义

Expression and significance of the lysinespecific demethylase 1 in gastric cancer tissues

    摘要
  • 摘要: 目的:检测胃癌及癌旁组织中的赖氨酸特异性去甲基化酶1(LSD1)、E钙黏蛋白的表达，探讨LSD1、E钙黏蛋白与胃癌患者的临床病理特征、预后之间的关系，以及LSD1与E钙黏蛋白表达的相关性。
    方法:采用病例对照研究方法。收集2008年6月至2009年6月中南大学湘雅医院收治80例胃癌患者手术切除的胃癌组织及癌旁组织。采用免疫组织化学染色检测手术标本中LSD1、E钙黏蛋白的表达情况。术后通过电话随访，了解患者生存情况。随访时间截至2015年6月。分析LSD1和E钙黏蛋白的表达及其与胃癌患者临床病理特征的关系，LSD1和E钙黏蛋白在胃癌组织中表达的相关性。分析LSD1、 E钙黏蛋白表达与胃癌患者预后的关系。计数资料的比较采用χ2检验，相关性采用Spearman等级相关分析，采用KaplanMeier法绘制生存曲线，Logrank检验进行生存分析。
    结果:LSD1在胃癌细胞及癌旁组织细胞中表达均定位于细胞核。其阳性表达率分别为67.5%(54/80)、43.8%(35/80)，两者比较，差异有统计学意义(χ2=9.141，P<0.05)。E钙黏蛋白在胃癌细胞及癌旁组织细胞中表达定位于细胞膜和细胞质。其阳性表达率分别为63.8%(51/80)、81.3%(65/80)，两者比较，差异有统计学意义(χ2=6.140，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83.3%(25/30)、76.0%(19/25)和40.0%(10/25)，在TNM分期的Ⅰ、Ⅱ、Ⅲ、Ⅳ期中分别为37.5%(6/16)、72.7%(16/22)、71.9%(23/32)和90.0%(9/10)，在无和有淋巴结转移中分别为36.4%(4/11)和72.5%(50/69)，几者比较，差异均有统计学意义(χ2= 12.870,9.425,4.111，P<0.05)。E钙黏蛋白在低、中、高分化的阳性表达率分别为53.3%(16/30)、56.0%(14/25)和84.0%(21/25)，在TNM分期的Ⅰ、Ⅱ、Ⅲ、Ⅳ期中分别为75.0%(12/16)、 63.6%(14/22)、71.9%(23/32)和20.0%(2/10)，在无和有淋巴结转移中分别为100.0%(11/11)和 58.0%(40/69)，在无和有远处转移中分别为70.0%(49/70)和20.0%(2/10)，几者比较，差异均有统计学意义(χ2=6.494,10.073,5.547,7.426，P<0.05)。LSD1与E钙黏蛋白在胃癌中的表达呈负相关(r= -0.355，P<0.05)。LSD1阳性表达的患者生存时间为(36.9±2.5)个月，5年总体生存率为31.1%；LSD1阴性表达的患者生存时间为(47.4±3.4)个月，5年总体生存率为56.0%，两者生存情况比较，差异有统计学意义(χ2=4.550，P<0.05)。E钙黏蛋白阳性表达的患者生存时间为(44.0±2.5)个月，5年总体生存率为46.7%；E钙黏蛋白阴性表达的患者生存时间为(32.6±3.5)个月，5年总体生存率为24.9%，两者生存情况比较，差异有统计学意义(χ2=7.306，P<0.05)。
    结论:LSD1在胃癌组织中较癌旁组织中阳性表达率高，在低分化胃癌及较晚TNM分期的胃癌组织中LSD1的表达率明显增高，而E钙黏蛋白的表达率则明显降低；二者的表达呈负相关。阳性表达LSD1及阴性表达E钙黏蛋白的胃癌患者预后可能更差。

     

    Abstract: Objective:To investigate the expressions and relationship between lysinespecific demethylase 1 (LSD1) and Ecadherin protein in gastric cancer tissues and adjacent normal tissues, and the correlation with the clinicopathological features and prognosis of patients with gastric cancer.
    Methods:The casecontrol study was adopted. The gastric cancer tissues and adjacent normal tissues were collected by surgical resection from 80 patients with gastric cancer who were admitted to the Xiangya Hospital of Central South University from June 2008 to June 2009. Expressions of LSD1 and Ecadherin protein were detected by immunohistochemistry (IHC). The followup of telephone interview was performed to detect survival of patients till June 2015. Relationships between the expressions of LSD1 and Ecadherin protein and clinicopathological features or prognosis of patients were analyzed. Comparison of count data and correlation were analyzed by the chisquare test and Spearman rank correlation analysis. Survival curve was drawn using the KaplanMeier method, and survival analysis was done using the Logrank test.
    Results:Expressions of LSD1 in cancer tissues and adjacent normal tissues were located at the cell nucleus. The positive expression rate of LSD1 was 67.5%(54/80) and 43.8%(35/80) in cancer tissues and adjacent normal tissues, respectively, with a significant difference (χ2=9.141, P<0.05). Expressions of Ecadherin protein in cancer tissues and adjacent normal tissues were located at the cell membrane and cytoplasm. The positive expression rate of Ecadherin was 63.8%(51/80) and 81.3%(65/80) in cancer tissues and adjacent normal tissues, respectively, with a significant difference (χ2=6.140, P<0.05). The positive expression rate of LSD1 was 83.3%(25/30), 76.0%(19/25) and 40.0%(10/25) in the low, moderate and highdifferentiated tumors, 37.5%(6/16), 72.7%(16/22), 71.9%(23/32) and 90.0% (9/10) in the Ⅰ, Ⅱ, Ⅲ and Ⅳ stages of TNM stage, 36.4%(4/11) and 72.5%(50/69) in patients without and with lymph node metastasis, respectively, showing significant differences (χ2=12.870, 9.425, 4.111, P<0.05). The positive expression rate of Ecadherin protein was 53.3%(16/30), 56.0% (14/25) and 84.0%(21/25) in the low, moderate and  highdifferentiated tumors, 75.0%(12/16), 63.6%(14/22), 71.9%(23/32) and 20.0% (2/10) in the Ⅰ, Ⅱ, Ⅲ and Ⅳ  stages of TNM stage, 100.0%(11/11)and 58.0%(40/69) in patients without and with lymph node metastasis,70.0%(49/70) and 20.0%(2/10) in patients without and with distant metastasis,  respectively, showing significant differences (χ2=6.494, 10.073, 5.547, 7.426, P<0.05). There was a negative correlation in expressions between LSD1 and Ecadherin protein (r=-0.355, P<0.05). The survival time and 5year overall survival rate of patients with positive and negative expressions of LSD1 were (36.9±2.5)months and 31.1%, (47.4±3.4)months and 56.0%, respectively, showing a significant difference (χ2=4.550, P<0.05). The survival time and 5year overall survival rate of the patients with positive and negative expressions of Ecadherin protein were (44.0±2.5)months and 46.7%, (32.6±3.5)months and 24.9%, respectively, showing a significant difference (χ2=7.306, P<0.05).
    Conclusions:Positive expression of LSD1 in gastric cancer tissues is higher than that in adjacent normal tissues. There are increased expression of LSD1 and reduced expression of Ecadherin protein in lowdifferentiated gastric cancer tissues and high TNM stage, showing a negative correlation between them. Positive expression of LSD1 and negative expression of Ecadherin protein may indicate a poor prognosis.

     

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