切换至 "中华医学电子期刊资源库"
高级检索
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:
全文 ( ) 下载PDF ( ) 导出引用
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/OL]. 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/OL]. 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
1
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69 (1): 7-34.
2
宁洪叶，蒋贤高，施伎蝉，等. 结核分枝杆菌感染对非小细胞肺癌患者调节性免疫细胞的负向调节作用[J/CD]. 中华危重症医学杂志（电子版），2019，12(4):240-244.

URL    
3
Souquet PJ, Couraud S. Immune checkpoint inhibitors: a game changer for metastatic non-small-cell lung cancer[J]. Lancet Oncol, 2019, 20 (10): 1334-1335.
4
Johnson MB, Sun X, Kodani A, et al. Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size[J]. Nature, 2018, 556 (7701): 370-375.
5
喻昊骏. TPX2与ASPM在前列腺癌中表达的相关性及临床意义[D]. 广州：广州医科大学，2018.
6
Shi Z, Xiao Z, Hu L, et al. The genetic association between type 2 diabetic and hepatocellular carcinomas[J]. Ann Transl Med, 2020, 8 (6): 380.
7
Lin S, Zhang R, An X, et al. LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells[J]. Oncogenesis, 2019, 8 (11): 60.
8
Zhai S, Lin S, Lin Z, et al. eIF4EBP3 was downreg-ulated by methylation and acted as a tumor suppressor by targeting eIF4E / β-catenin in gastric cancer[J]. Gastric Cancer, 2020, 23 (3): 483-496.
9
李伟琴. 口腔鳞状细胞癌患者血清Cyfra 21-1和癌胚抗原含量检测的临床意义[J/CD]. 中华危重症医学杂志（电子版），2019，12(2):126-127.

URL    
10
Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review[J]. JAMA, 2019, 322 (8): 764-774.
11
张秀义，许浩然，孙亚东. 非小细胞肺癌组织Beclin1、LC3表达变化及其临床意义[J]. 山东医药，2018，58(48):66-69.
12
Jiang K, Rezabkova L, Hua S, et al. Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex[J]. Nat Cell Biol, 2017, 19 (5): 480-492.
13
Gai M, Bianchi FT, Vagnoni C, et al. ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules[J]. EMBO Rep, 2017, 18 (10): 1870.
14
梁文涛. 胶质瘤中ASPM与MGMT表达及其临床意义[D]. 兰州：兰州大学，2015.
15
Timaner M, Shaked Y. Elucidating the roles of ASPM isoforms reveals a novel prognostic marker for pancreatic cancer[J]. J Pathol, 2019, 250 (2): 123-125.
16
Pai VC, Hsu CC, Chan TS, et al. ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling[J]. Oncogene, 2019, 38 (8): 1340-1353.
17
Wang F, Li J, Liu J, et al. Controversial role of the possible oxyntic stem cell marker ASPM in gastric cancer[J]. J Pathol, 2017, 241 (4): 559-561.
18
Selamat SA, Chung BS, Girard L, et al. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression[J]. Genome Res, 2012, 22 (7): 1197-1211.
19
Hou J, Aerts J, den Hamer B, et al. Gene expression-based classification of non-small cell lung carcinomas and survival prediction[J]. PLoS One, 2010, 5 (4): e10312.
20
Okayama H, Kohno T, Ishii Y, et al. Identification of genes upregulated in ALK-positive and EGFR / KRAS / ALK-negative lung adenocarcinomas[J]. Cancer Res, 2012, 72 (1): 100-111.
21
Gyorffy B, Surowiak P, Budczies J, et al. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer[J]. PLoS One, 2013, 8 (12): e82241.
[1] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[2] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[3] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[4] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[5] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[6] 顾雯, 凌守鑫, 唐海利, 甘雪梅. 两种不同手术入路在甲状腺乳头状癌患者开放性根治性术中的应用比较[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 687-690.
[7] 付成旺, 杨大刚, 王榕, 李福堂. 营养与炎症指标在可切除胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 704-708.
[8] 梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[9] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[10] 李伟, 宋子健, 赖衍成, 周睿, 吴涵, 邓龙昕, 陈锐. 人工智能应用于前列腺癌患者预后预测的研究现状及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 541-546.
[11] 关小玲, 周文营, 陈洪平. PTAAR在乙肝相关慢加急性肝衰竭患者短期预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 841-845.
[12] 张润锦, 阳盼, 林燕斯, 刘尊龙, 刘建平, 金小岩. EB病毒相关胆管癌伴多发转移一例及国内文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 865-869.
[13] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[14] 董佳, 王坤, 张莉. 预后营养指数结合免疫球蛋白、血糖及甲胎蛋白对HBV 相关慢加急性肝衰竭患者治疗后预后不良的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 555-559.
[15] 王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号