Expression and clinical significance of SMAD9 in lung adenocarcinoma

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 (P < 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 (P < 0.05). The down-regulation of SMAD9 expression was closely correlated with N grade and tumor grade (P < 0.05). ROC curve analysis indicated that the mRNA expression of SMAD9 was a sensitive indicator of lung adenocarcinoma (AUC=0.903, 95%CI=0.868~0.938, P < 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 (P < 0.05). Overexpression of SMAD9 inhibited the proliferation of lung adenocarcinoma cells (P < 0.01), and the proliferation of HBE cells was significantly enhanced after interfering with SMAD9 expression as compared with the control cells (P < 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.

Keywords

• smad9
• lung adenocarcinoma
• tcga
• gene expression
• postoperative survival