中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (10): 791-797.doi: 10.19401/j.cnki.1007-3639.2020.10.010

• 论著 • 上一篇    下一篇

Prospero相关同源异形盒蛋白1在非小细胞肺癌中的表达及意义

杨 光 1 ,张 昆 1 ,王 俊 2   

  1. 1. 淄博市第一医院心胸外科,山东 淄博 255200 ;
    2. 中国人民解放军济南军区总医院肿瘤科,山东 济南 250031
  • 出版日期:2020-10-30 发布日期:2020-11-12
  • 通信作者: 王 俊 E-mail: quan26402979@163.com
  • 基金资助:
    国家自然科学基金(81572875)。

Expression of prospero-related homeobox protein 1 and its significance in non-small cell lung cancer

YANG Guang 1 , ZHANG Kun 1 , WANG Jun 2 #br#   

  1. 1. Department of Cardiothoracic Surgery, Zibo First Hospital, Zibo 255200, Shandong Province, China; 2. Department of Oncology, General Hospital of Jinan Military Region, People’s Liberation Army, Jinan 250031, Shandong Province, China
  • Published:2020-10-30 Online:2020-11-12
  • Contact: WANG Jun E-mail: quan26402979@163.com

摘要: 背景与目的:Prospero相关同源异形盒蛋白1(prospero-related homeobox 1,PROX1)是一种高度保守的转录调节因子,参与多种肿瘤的发生、发展。探讨PROX1在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及意义。方法:免疫组织化学法检测2011年1月—2013年6月在淄博市第一医院手术切除的86例NSCLC癌组织及其配对的癌旁组织中PROX1的表达;蛋白质印迹法(Western blot)检测人NSCLC细胞系A549、H460、H1229、H358和人支气管上皮细胞Beas-2b中PROX1的表达。采用克隆形成实验、细胞计数试剂盒(cell counting kit-8,CCK-8)实验、transwell侵袭和迁移实验检测敲降PROX1对A549细胞生物学功能的影响。生存分析用Kaplan-Meier法,NSCLC患者生存预后的影响因素用COX比例风险回归模型。结果:癌组织中PROX1阴性、弱阳性、中等阳性、强阳性分别6例、25例、20例、35例;癌旁组织中分别48例、27例、8例、3例,癌组织中PROX1阳性表达率明显高于癌旁组织(P<0.05)。与Beas-2b相比,A549、H460、H1229和H358细胞系中PROX1蛋白水平明显较高(P均<0.05)。PROX1高表达组淋巴结转移率和TNM分期为Ⅲ~Ⅳ期的占比明显高于低表达组(P<0.05)。TNM分期为Ⅲ~Ⅳ期、淋巴结转移、远处转移和PROX1高表达是NSCLC患者不良生存预后的独立影响因素(P<0.05)。PROX1高表达组生存时间明显短于低表达组(P<0.05)。敲降PROX1后A549细胞PROX1蛋白表达水平、克隆数目、培养第72和96 h时细胞增殖的吸光度(D)值、侵袭和迁移细胞数量明显降低(P<0.05)。结论:PROX1在NSCLC发生、发展中可能起到重要作用,敲降PROX1基因可以抑制NSCLC细胞的增殖、侵袭和迁移,PROX1高表达可能预示患者不良生存预后。

关键词: Prospero相关同源异形盒蛋白1, 非小细胞肺癌, 增殖, 侵袭, 迁移

Abstract: Background and purpose: Prospero-related homeobox protein 1 (PROX1) is a highly conserved transcription regulator, which is involved in the occurrence and development of many types of tumors. The purpose of this study was to investigate the expression of PROX1 and its significance in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical method was used to detect the expression of PROX1 in 86 NSCLC cancer tissues and their matched adjacent tissues from Jan. 2011 to Jun. 2013 in the Zibo First Hospital. The expression of PROX1 in human NSCLC cell lines A549, H460, H1229, H358 and human bronchial epithelial cells Beas-2b was detected by Western blot. Kaplan-Meier method was used for survival analysis, and COX proportional risk regression model was used to analyze the influencing factors of survival prognosis in NSCLC patients. Results: There were 6 PROX1 negative, 25 weak positive, 20 medium positive and 35 strong positive cases in cancer tissues, whereas there were 48 PROX1 negative, 27 weak positive, 8 medium positive and 3 strong positive cases in para-cancerous tissues, respectively. The positive expression rate of PROX1 in cancer tissues was significantly higher than that in para-cancerous tissues (P<0.05). Compared with Beas-2b, the expression of PROX1 protein in A549, H460, H1229 and H358 cells was significantly higher (P<0.05). The proportion of lymph node metastasis and TNM stage Ⅲ-Ⅳ in PROX1 high expression group was significantly higher than that in low expression group (P<0.05). TNM stage Ⅲ-Ⅳ , lymph node metastasis, distant metastasis and high expression of PROX1 were independent influencing factors of poor survival and prognosis in NSCLC (P<0.05). The survival time of PROX1 high expression group was significantly lower than that of low expression group (P<0.05). After knockdown of PROX1, PROX1 protein expression levels, the clone number of A549 cells, the D value of cell proliferation and the number of invasion and migration cells decreased significantly (P<0.05). Conclusion: PROX1 may play an important role in the occurrence and development of NSCLC. Knockdown of PROX1 gene could inhibit the proliferation, invasion and migration of NSCLC cells. High PROX1 expression might predict the poor prognosis of patients.

Key words: Prospero-related homeobox protein 1, Non-small cell lung cancer, Proliferation, Invasion, Migration