SMAD9基因在肺腺癌中的表达及临床意义

陈东姣; 刘文斌; 陈洪强; 刘晋祎; 杨惠芳; 曹佳

doi:10.16016/j.1000-5404.201910191

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SMAD9基因在肺腺癌中的表达及临床意义

临床医学 | 更新时间：2026-01-09

- SMAD9基因在肺腺癌中的表达及临床意义
- Expression and clinical significance of SMAD9 in lung adenocarcinoma
- 第三军医大学学报 2020年42卷第7期页码：699-707
- 作者机构：
  
  1.750004 银川，宁夏医科大学公共卫生与管理学院劳动卫生与环境卫生学教研室
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系毒理学研究所
- 作者简介：
  
  [ 杨惠芳. E-mail:joyceyhf@163.com YANG Hui-fang, E-mail:joyceyhf@163.com
  [ 曹佳. E-mail:caojia1962@126.com CAO Jia, E-mail:caojia1962@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81573114);国家自然科学基金面上项目(81872659)
- DOI：10.16016/j.1000-5404.201910191
  中图分类号： R394.3;R730.23;R734.2
- 收稿：2019-10-29，
  
  修回：2020-01-10，
  
  纸质出版：2020-04-15
- 稿件说明：
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陈东姣, 刘文斌, 陈洪强, 等. SMAD9基因在肺腺癌中的表达及临床意义[J]. 第三军医大学学报, 2020,42(7):699-707.

Dongjiao CHEN, Wenbin LIU, Hongqiang CHEN, et al. Expression and clinical significance of SMAD9 in lung adenocarcinoma[J]. Journal of Third Military Medical University, 2020, 42(7): 699-707.
陈东姣, 刘文斌, 陈洪强, 等. SMAD9基因在肺腺癌中的表达及临床意义[J]. 第三军医大学学报, 2020,42(7):699-707. DOI： 10.16016/j.1000-5404.201910191.

Dongjiao CHEN, Wenbin LIU, Hongqiang CHEN, et al. Expression and clinical significance of SMAD9 in lung adenocarcinoma[J]. Journal of Third Military Medical University, 2020, 42(7): 699-707. DOI： 10.16016/j.1000-5404.201910191.

摘要

目的

探讨SMAD9基因在肺腺癌中的表达变化与临床病理指标以及术后生存之间的关联，为肺腺癌的筛查及其预后提供参考依据。

方法

基于肿瘤基因图谱(the Cancer Genome Atlas，TCGA)数据库收集的数据，分析SMAD9基因在肺腺癌患者肿瘤组织(510例)和癌旁正常组织(59例)中的表达情况以及与临床病理指标和术后生存的关系。收集肺腺癌患者的肿瘤组织及癌旁正常组织、3-甲基胆蒽(3-MCA)诱导的HBE恶性转化细胞、肺腺癌细胞株，采用qRT-PCR以及Western blot方法检测SMAD9基因的mRNA及蛋白表达水平。采用CCK-8法检测SMAD9过表达和干扰对细胞增殖的影响。

结果

TCGA数据库分析结果显示，在肺腺癌患者中，肿瘤组织的SMAD9基因的mRNA表达显著低于癌旁正常组织(

0.01)。qRT-PCR以及Western blot结果都显示，SMAD9基因在3-MCA诱导的HBE恶性转化细胞中呈下调趋势，且在恶转细胞中随着恶转代数增加下调越明显；该基因在肺腺癌组织、多株肺腺癌细胞中的表达均呈现显著下调(

0.05)。SMAD9基因的表达与N分期及肿瘤分期高度相关(

0.05)。ROC曲线分析结果显示，SMAD9基因mRNA的表达是一个灵敏度较好的肺腺癌分子筛查标志物(AUC=0.904，95%

=0.869~0.938，

0.001)。Kaplan-Meier分析结果显示，肺腺癌患者中，SMAD9基因低表达患者生存时间显著低于高表达患者的生存时间(

0.05)。过表达SMAD9基因抑制肺腺癌细胞增殖(

0.01)，干扰SMAD9表达后HBE细胞增殖能力显著增强(

0.01)。

结论

SMAD9基因在肺腺癌发生、发展过程中表达下调，该基因的表达对肺腺癌患者的筛查和术后生存具有较好的参考价值。

Abstract

Objective

To investigate the mRNA expression of SMAD9 in lung adenocarcinoma

and its relationship with clinicopathological parameters

survival and prognosis

so as to provide some valuable references for the screening and postoperative survival.

Methods

The expression of SMAD9 in tumor tissues (510 cases) and adjacent normal tissues (59 cases) of lung adenocarcinoma patients and its relationship with clinicopathological parameters and postoperative survival were analyzed based on the Cancer Genome Atlas (TCGA) database. The expression of SMAD9 in tumor tissues and adjacent normal tissues of lung adenocarcinoma patients

HBE malignant transformed cells induced by 3-MCA and lung adenocarcinoma cells were detected by quantitative real-time RT-PCR (qRT-PCR) and Western blotting. The effect of SMAD9 overexpression and interference on cell proliferation was detected by CCK-8 assay.

Results

The mRNA expression analysis of SMAD9 in TCGA database showed that the expression of SMAD9 was significantly lower in lung adenocarcinoma than adjacent normal tissues (

0.01). The results of qRT-PCR and Western blotting also showed that the expression of SMAD9 was significantly down-regulated in 3-MCA-induced HBE malignant transformed cells and lung adenocarcinoma tissues and cell lines (

0.05). The down-regulation of SMAD9 expression was closely correlated with N grade and tumor grade (

0.05). ROC curve analysis indicated that the mRNA expression of SMAD9 was a sensitive indicator of lung adenocarcinoma (AUC=0.903

95%

=0.868~0.938

0.001). Kaplan-Meier analysis displayed that the survival time of patients with low expression of SMAD9 was significantly shorter than those with high expression (

0.05). Overexpression of SMAD9 inhibited the proliferation of lung adenocarcinoma cells (

0.01)

and the proliferation of HBE cells was significantly enhanced after interfering with SMAD9 expression as compared with the control cells (

0.01).

Conclusion

SMAD9 gene expression is down-regulated in the incidence and development of lung adenocarcinoma. The expression of SMAD9 may be of great value for the screening and postoperative survival of lung adenocarcinoma patients.

关键词

Keywords

references

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