Expression and clinical significance of SMAD9 in lung adenocarcinoma

Dongjiao CHEN; Wenbin LIU; Hongqiang CHEN; Jinyi LIU; Huifang YANG; Jia CAO

doi:10.16016/j.1000-5404.201910191

您当前的位置：

首页 >

文章列表页 >

Expression and clinical significance of SMAD9 in lung adenocarcinoma

Clinical Medicine | 更新时间：2026-01-09

- Expression and clinical significance of SMAD9 in lung adenocarcinoma
- Journal of Third Military Medical University Vol. 42, Issue 7, Pages: 699-707(2020)
- 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：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81573114);the General Program of National Natural Science Foundation of China(81872659)
- DOI：10.16016/j.1000-5404.201910191
  CLC： R394.3;R730.23;R734.2
- Received：29 October 2019，
  
  Revised：2020-01-10，
  
  Published：15 April 2020
- 稿件说明：
移动端阅览
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：

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

BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI:10.3322/caac.21492.

郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志, 2019, 41(1):19-28. DOI:10.3760/cma.j.issn.0253-3776.2019.01.005.

ZHENG R S, SUN K X, ZHANG S W, et al . Report of cancer epidemiology in China, 2015[J ] . Chin J Oncol, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.

李祥春, 刘子玲, 丛晓凤, 等.肺鳞状细胞癌基因靶点的研究进展[J].癌症进展, 2019, 17(8): 887-889, 904. DOI:10.11877/j.issn.1672-1535. 2019.17.08.05.

LI X C, LIU Z L, CONG X F, et al . Advances in research on lung squamous cell oncogene targets[J ] . Oncol Prog, 2019, 17(8): 887-889, 904. DOI:10.11877/j.issn.1672-1535.2019.17.08.05.

PASERO M, GIOVARELLI M, BUCCI G, et al . Bone morphogenetic protein/SMAD signaling orients cell fate decision by impairing KSRP-dependent microRNA maturation[J ] . Cell Rep, 2012, 2(5): 1159-1168. DOI:10.1016/j.celrep.2012.10.020.

HESTER M, THOMPSON J C, MILLS J, et al . Smad1 and Smad8 function similarly in mammalian central nervous system development[J ] . Mol Cell Biol, 2005, 25(11): 4683-4692. DOI:10.1128/MCB.25.11.4683-4692.2005.

PANGAS S A, LI X H, UMANS L, et al . Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice[J ] . Mol Cell Biol, 2008, 28(1):248-257. DOI:10.1128/MCB. 01404-07.

RAY B N, LEE N Y, HOW T, et al . ALK5 phosphorylation of the endoglin cytoplasmic do main regulates Smad1/5/8 signaling and endothelial cell migration[J ] . Carcinogenesis, 2010, 31(3): 435-441. DOI:10.1093/carcin/bgp327.

HUERTAS A, TU L, GUIGNABERT C. New targets for pulmonary arterial hypertension: going beyond the currently targeted three pathways[J]. Curr Opin Pulm Med, 2017, 23(5): 377-385. DOI:10.1097/MCP.0000000000000404.

KANG G H, LEE S, CHO N Y, et al . DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis[J ] . Lab Invest, 2008, 88(2): 161-170. DOI:10.1038/labinvest.3700707.

KOKAJI E, SHIMOMURA A, MINAMISAKA T, et al . Endoglin (CD105) and SMAD4 regulate spheroid formation and the suppression of the invasive ability of human pancreatic cancer cells[J ] . Int J Oncol, 2018, 52(3): 892-900. DOI:10.3892/ijo.2018.4262.

ELSAFADI M, SHINWARI T, AL-MALKI S, et al . Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation[J ] . Sci Rep, 2019, 9(1): 4977. DOI:10.1038/s41598-019-41543-0.

CHEN H Q, ZHAO J, LI Y, et al . Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells[J ] . Toxicol Lett, 2018, 289: 42-53. DOI:10.1016/j.toxlet.2018.03.003.

KATAKAWA Y, FUNABA M, MURAKAMI M. Smad8/9 is regulated through the BMP pathway[J]. J Cell Biochem, 2016, 117(8): 1788-1796. DOI:10.1002/jcb.25478.

SPINELLI R, PIROLA A, REDAELLI S, et al . Identification of novel point mutations in splicing sites integrating whole-exome and RNA-seq data in myeloproliferative diseases[J ] . Mol Genet Genomic Med, 2013, 1(4): 246-259. DOI:10.1002/mgg3.23.

SCHULTEN H J, AL-MANSOURI Z, BAGHALLAB I, et al . Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid[J ] . BMC Genomics, 2015, 16(Suppl 1): S7. DOI:10.1186/1471-2164-16-S1-S7.

CHIBA T, ISHISAKI A, KYAKUMOTO S, et al . Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression[J ] . Oncol Rep, 2017, 37(2): 713-720. DOI:10.3892/or.2016.5338.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Screening and validation of tsRNAs associated with lung adenocarcinoma

Clinical characteristics and survival analysis of rare mutations in locally advanced or metastatic lung adenocarcinoma

Preparation and identification of ¹³¹I-RP215 McAb molecular probe and its application for radioimmunoimaging in lung adenocarcinoma-bearing nude mice

Functional study of LncRNA MUC5B-AS1 in lung adenocarcinoma cell lines

Prognostic prediction of lung adenocarcinoma based on transcriptomic data and stacked supervised autoencoder

Related Author

LU Chunli

SHAN Yifan

XIE Weijia

XIA Tingting

XIANG Ying

WU Na

WU Long

BAI Li

Related Institution

Department of Epidemiology， Faculty of Military Preventive Medicine， Army Medical University （Third Military Medical University）， Chongqing, PLA Key Laboratory of Respiratory Diseases， Second Affiliated Hospital， Army Medical University （Third Military Medical University）

Institute of Respiratory Diseases, PLA Key Laboratory of Respiratory Diseases， Second Affiliated Hospital， Army Medical University （Third Military Medical University）

Department of Respiratory Disease and Critical Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine

Department of Nuclear Medicine, the First Affiliated Hospital of Chongqing Medical University

Department of Epidemiology, School of Public Health, Guizhou Medical University

⁰