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中华危重症医学杂志(电子版)

中华危重症医学杂志(电子版) ›› 2020, Vol. 13 ›› Issue (03) : 176 -180. doi: 10.3877/cma.j.issn.1674-6880.2020.03.004

所属专题： 文献；

论著

人类异常纺锤体样小头畸形相关蛋白在非小细胞肺癌中的表达及其临床意义
张锐1, 沈雅芳2, 安肖霞3, 林双4,†()   
  1. 1. 310008　杭州，杭州市五云山疗养院内科
    2. 310003　杭州，浙江大学医学院附属第一医院肺移植科
    3. 310003　杭州，浙江大学医学院附属第一医院麻醉科
    4. 310003　杭州，浙江大学医学院附属第一医院胸外科
  • 收稿日期:2020-01-21 出版日期:2020-06-01
  • 通信作者: 林双
  • 基金资助:
    国家自然科学基金项目(61976075); 浙江省自然科学基金项目(LY19H160057); 浙江省公益技术研究计划项目(LGD19H030003、GF18H180028); 浙江省中医药科研计划项目(2019ZA070)

Expression of abnormal spindle-like microcephaly associated protein in non-small cell lung cancer and its clinical significance

Rui Zhang1, Yafang Shen2, Xiaoxia An3, Shuang Lin4,†()   

  1. 1. Department of Internal Medicine, the Wuyunshan Sanatorium of Hangzhou, Hangzhou 310008, China
    2. Department of Lung Transplantation, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
    3. Department of Anesthesiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
    4. Department of Thoracic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
  • Received:2020-01-21 Published:2020-06-01
  • Corresponding author: Shuang Lin
  • About author:
    Corresponding author: Lin Shuang, Email:
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引用本文：

张锐, 沈雅芳, 安肖霞, 林双. 人类异常纺锤体样小头畸形相关蛋白在非小细胞肺癌中的表达及其临床意义[J]. 中华危重症医学杂志(电子版), 2020, 13(03): 176-180.

Rui Zhang, Yafang Shen, Xiaoxia An, Shuang Lin. Expression of abnormal spindle-like microcephaly associated protein in non-small cell lung cancer and its clinical significance[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2020, 13(03): 176-180.

目的

探讨非小细胞肺癌（NSCLC）患者肿瘤组织和癌旁组织中人类异常纺锤体样小头畸形相关蛋白（ASPM）的表达情况及其与患者临床病理参数和预后的关系。

方法

收集175例随访满5年的NSCLC患者术后石蜡标本，包括肿瘤组织和癌旁组织，采用免疫组织化学染色法检测各组织中ASPM的表达情况。比较ASPM不同表达水平患者的年龄、性别比、分化程度构成比、吸烟史、病理类型、肿瘤大小、淋巴结转移及TNM分期构成比；绘制Kaplan-Meier生存曲线，采用log-rank检验比较NSCLC患者的5年总生存率；采用Cox回归模型分析影响NSCLC患者预后的危险因素。

结果

免疫组织化学染色结果显示，64.57%（113 / 175）的肿瘤组织标本中呈ASPM高表达，而癌旁组织中仅有22.29%（39 / 175）呈ASPM高表达，NSCLC患者肿瘤组织中的ASPM高表达占比显著高于癌旁组织（ χ2 = 63.683，P < 0.001）。根据肿瘤组织标本染色结果，将175例NSCLC患者标本分为ASPM低表达组（62例）和ASPM高表达组（113例）。两组患者肿瘤大小（ χ2 = 5.060，P = 0.024）、淋巴结转移（ χ2 = 3.998，P = 0.046）及TNM分期构成比（ χ2 = 5.427，P = 0.020）比较，差异均有统计学意义。Kaplan-Meier生存曲线结果显示，ASPM低表达组NSCLC患者5年总生存率显著优于ASPM高表达组（ χ2 = 5.040，P = 0.025）。将肿瘤大小、淋巴结转移、TNM分期及ASPM表达纳入Cox回归分析，结果显示TNM分期[风险比（HR）= 3.883，95%置信区间（CI）（1.616，9.330），P = 0.005]和ASPM表达[HR = 3.845，95%CI（1.795，8.236），P = 0.008]是影响NSCLC预后的危险因素。

结论

ASPM在NSCLC患者肿瘤组织中呈高表达，且其表达水平是影响NSCLC患者预后的危险因素。

关键词: 人类异常纺锤体样小头畸形相关蛋白, 癌，非小细胞肺, 免疫组织化学染色法, 预后
Objective

To investigate the expression of abnormal spindle-like microcephaly associated protein (ASPM) in tumor and paracancerous tissues of patients with non-small cell lung cancer (NSCLC) and its relationship with their clinicopathological parameters and prognosis.

Methods

Paraffin samples including tumor and paracancerous tissues were collected from 175 NSCLC patients who had been followed up for 5 years and the expression of ASPM was detected by immunohistochemical staining in each tissue. The age, sex ratio, differentiation ratio, smoking history, pathological type, tumor size, lymph node metastasis and TNM staging ratio were compared among patients with different ASPM expression levels. The Kaplan-Meier survival curve was drawn and the 5-year overall survival rate of NSCLC patients was compared by the log-rank test. The Cox regression model was used to analyze the risk factors for the prognosis of NSCLC patients.

Results

The immunohistochemical staining revealed that 64.57% (113 / 175) of tumor tissue samples showed high expression of ASPM, while only 22.29% (39 / 175) of adjacent tissues showed high expression of ASPM. The high expression ratio of ASPM in tumor tissues of NSCLC patients was significantly higher than that in adjacent tissues ( χ2 = 63.683, P < 0.001). The 175 NSCLC patients were divided into an ASPM low expression group (n = 62) and an ASPM high expression group (n = 113) according to the staining results of tumor tissue samples. The tumor size ( χ2 = 5.060, P = 0.024), lymph node metastasis ( χ2 = 3.998, P = 0.046) and TNM staging ( χ2 = 5.427, P = 0.020) were statistically significantly different between these two groups. The Kaplan-Meier survival curve showed that the 5-year overall survival rate of NSCLC patients in the ASPM low expression group was significantly better than that in the ASPM high expression group ( χ2 = 5.040, P = 0.025). The tumor size, lymph node metastasis, TNM stage and ASPM expression were included in the Cox regression analysis, and the result showed the TNM stage [hazard ratio (HR) = 3.883, 95% confidence interval (CI) (1.616, 9.330), P = 0.005] and ASPM expression [HR = 3.845, 95%CI (1.795, 8.236), P = 0.008] were risk factors for the prognosis of NSCLC patients.

Conclusion

ASPM is highly expressed in the tumor tissues of NSCLC patients, and its expression is a risk factor for their prognosis.

Key words: Abnormal spindle-like microcephaly associated protein, Carcinoma, non-small cell lung, Immunohistochemistry staining, Prognosis
图1 NSCLC患者肺癌组织中ASPM表达情况
表1 两组NSCLC患者临床病理参数比较（例）
组别 例数 年龄 性别 分化程度 吸烟史
≤ 50岁 > 50岁 男 女 中、高分化 未分化及低分化 无 有
ASPM低表达组 62 34 28 26 36 27 35 28 34
ASPM高表达组 113 56 57 41 72 61 52 39 74
χ2值 ? 0.447 0.541 1.743 1.921
P值 ? 0.504 0.462 0.187 0.166
组别 例数 病理类型 肿瘤大小 淋巴结转移 TNM分期
腺癌 鳞癌 ≤ 2 cm > 2 cm 无 有 Ⅰ期 Ⅱ ~ Ⅲ期
ASPM低表达组 62 37 25 39 23 41 21 41 21
ASPM高表达组 113 55 58 51 62 57 56 54 59
χ2值 ? 1.945 5.060 3.998 5.427
P值 ? 0.163 0.024 0.046 0.020
图2 两组NSCLC患者的Kaplan-Meier生存曲线
表2 NSCLC患者预后影响因素的Cox回归分析
危险因素 回归系数 标准误 Wald值 P值 HR值 95%CI
肿瘤大小 0.119 0.221 6.721 0.209 2.409 0.322 ~ 2.391
淋巴结转移 0.340 0.261 3.567 0.712 2.865 1.436 ~ 5.716
TNM分期 0.521 0.042 12.761 0.005 3.883 1.616 ~ 9.330
ASPM表达 0.385 0.176 15.235 0.008 3.845 1.795 ~ 8.236
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