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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1121-1123

Overexpression of forkhead box M1 is associated poor survival in patients with nonsmall cell lung cancer


1 Department of Respiratory, Shandong University, Jinan 250014; Department of Respiratory, Weihai Municipal Hospital, Weihai 264200, Shandong, P.R. China
2 Department of Dermatology, Weihai Municipal Hospital, Weihai 264200, Shandong, P.R. China
3 Department of Cardiology, Weihai Municipal Hospital, Weihai 264200, Shandong, P.R. China
4 Department of Intensive Care Unit, Weihai Municipal Hospital, Weihai 264200, Shandong, P.R. China
5 Department of Respiratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, P.R. China

Date of Web Publication11-Dec-2018

Correspondence Address:
Yuanrong Ju
Department of Respiratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.203605

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 > Abstract 


Aims: The association between forkhead box M1 (FOXM1) and survival of nonsmall cell lung cancer (NSCLC) has been extensively investigated. However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to precisely estimate the association between FOXM1 and survival of NSCLC.
Materials and Methods: Studies were searched using the PubMed and EMBASE. The strength of the association was calculated with the hazard ratios (HRs) and respective 95% confidence intervals (CIs).
Results: Result of this meta-analysis showed that high expression of FOXM1 was significantly associated with shorter overall survival (OS) of NSCLC (HR = 1.82; 95% CI 1.45–2.29). In the stratified analysis by country, we found that the expression of FOXM1 was significantly associated with shorter OS in Chinese NSCLC patients (HR = 1.82; 95% CI 1.45–2.29). In addition, high expression of FOXM1 decreased the OS in patients with surgery (HR = 1.88; 95% CI 1.37–2.58). Furthermore, the results were still positive in both large sample size studies and small sample size studies.
Conclusions: This meta-analysis showed that overexpression of FOXM1 might be associated with shorter OS of NSCLC patients.

Keywords: Forkhead box M1, nonsmall cell lung cancer, overall survival


How to cite this article:
Liu B, Su F, Lin R, Teng H, Ju Y. Overexpression of forkhead box M1 is associated poor survival in patients with nonsmall cell lung cancer. J Can Res Ther 2018;14, Suppl S5:1121-3

How to cite this URL:
Liu B, Su F, Lin R, Teng H, Ju Y. Overexpression of forkhead box M1 is associated poor survival in patients with nonsmall cell lung cancer. J Can Res Ther [serial online] 2018 [cited 2019 Sep 17];14:1121-3. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1121/203605




 > Introduction Top


Lung cancer is classified into two main histologic subtypes: Small cell lung cancer (SCLC) and non-SCLC (NSCLC) which is the most common type accounting for 85% of all lung cancer cases. The pathogenesis of NSCLC is still limited, and effective indicators for early diagnosis of NSCLC are lacking.

The protein forkhead box M1 (FOXM1), a member of the FOX family of transcription factors, is widely expressed in embryonic tissues.[1] Controlled FOXM1 expression and activity provide a balanced transcriptional program to ensure proper growth and maturation throughout embryonic and fetal development, as well as during adult tissue homeostasis and repair.[2] Oncogenic transcription factor FOXM1 is overexpressed in the majority of human cancers. In addition, FOXM1 has been implicated in cell migration, invasion, angiogenesis, and metastasis.[3]

The association between FOXM1 and survival of NSCLC has been extensively investigated.[4],[5],[6],[7],[8],[9],[10],[11] However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to precisely estimate the association between FOXM1 and survival of NSCLC.


 > Materials and Methods Top


Publication search

Studies were searched by using the PubMed and EMBASE. The search terms were “forkhead box M1” and “non-small cell lung cancer.” Additional studies were identifed by a hand search from the reference of original studies or review articles on this topic. There was no language restriction.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) The diagnosis of NSCLC was confirmed by pathology; (2) the research was a cohort study; (3) the study focused on the association between FOXM1 and survival of NSCLC. The exclusion criteria were as follows: (1) The NSCLC patients were not confirmed by pathology; (2) animal studies; (3) reviews or abstracts.

Data extraction

The following data were recorded from each article:First author, years of publication, study design, country of participants, age, type of NSCLC, surgery, outcome, duration of follow-up, numbers of cases and controls. The data were extracted by two of the authors independently. Discrepancies between these two authors were resolved by discussion.

Statistical analysis

The strength of association was assessed by calculating hazard ratio (HR) with 95% confidence interval (CI). A statistical test for heterogeneity was performed based on the Q statistic. The P > 0.10 of the Q-test indicated a lack of heterogeneity among studies. Stratified analysis was performed by country, surgery, and sample size. All statistical tests were performed with the software Review Manager. P < 0.05 was considered statistically significant.


 > Results Top


Literature search

A total of 7 studies with 824 cases on the association between FOXM1 and survival of NSCLC were included in this meta-analysis. There were six studies of Chinese populations and one study of the Korean population. The characteristics of each study are presented in [Table 1].
Table 1: Characteristics of the included studies

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Meta-analysis

The result of this meta-analysis showed that high expression of FOXM1 was significantly associated with shorter overall survival (OS) of NSCLC (HR = 1.82; 95% CI 1.45–2.29) [Figure 1]. In the stratified analysis by country, we found that the expression of FOXM1 was significantly associated with shorter OS in Chinese NSCLC patients (HR = 1.82; 95% CI 1.45–2.29). In addition, high expression of FOXM1 decreased the OS in patients with surgery (HR = 1.88; 95% CI 1.37–2.58). Furthermore, the results were still positive in both large sample size studies and small sample size studies [Table 2].
Figure 1: The association between the expression of forkhead box M1 and overall survival of nonsmall cell lung cancer

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Table 2: Results of the meta-analysis

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 > Discussion Top


We performed a systematic search of the literature and combined the available results in this meta-analysis. High expression of FOXM1 has been studied extensively about the relationship with NSCLC survival. Previous results were contradictory. We thus performed a meta-analysis. We found that high expression of FOXM1 was significantly associated with shorter OS of NSCLC, Chinese NSCLC patients, and patients with surgery.

Kong et al. suggested that FOXM1 regulated by the ERK pathway can mediate transforming growth factor-β1-induced epithelial–mesenchymal transition in NSCLC and is a potential target for the treatment of NSCLC.[12] Xu et al. indicated that FOXM1 played an important role in the resistance of NSCLC cells to gefitinib in vitro.[13] Gialmanidis et al. found that overexpression of FOXM1 in NSCLC was also significantly correlated with PTCH1, SMO, and GLI1 expression.[14] Kim et al. found that FOXM1 stimulated the proliferation of tumor cells during progression of NSCLC.[4]

Some limitations should be addressed. First, more studies with large sample sizes are needed to further identify the result. Second, because small negative studies are less likely to published, the possibility of publication bias cannot be ruled out completely.


 > Conclusions Top


This meta-analysis showed that overexpression of FOXM1 might be associated with shorter OS of NSCLC patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Korver W, Roose J, Clevers H. The winged-helix transcription factor trident is expressed in cycling cells. Nucleic Acids Res 1997;25:1715-9.  Back to cited text no. 1
    
2.
Katoh M, Igarashi M, Fukuda H, Nakagama H, Katoh M. Cancer genetics and genomics of human FOX family genes. Cancer Lett 2013;328:198-206.  Back to cited text no. 2
    
3.
Halasi M, Gartel AL. Targeting FOXM1 in cancer. Biochem Pharmacol 2013;85:644-52.  Back to cited text no. 3
    
4.
Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, et al. The forkhead box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res 2006;66:2153-61.  Back to cited text no. 4
    
5.
Yang DK, Son CH, Lee SK, Choi PJ, Lee KE, Roh MS. Forkhead box M1 expression in pulmonary squamous cell carcinoma: Correlation with clinicopathologic features and its prognostic significance. Hum Pathol 2009;40:464-70.  Back to cited text no. 5
    
6.
Liu YQ, Guo RH, Liu LK, Gao W, Zhu CJ, Wei J, et al. Correlation between expression of forkhead box M1 (FOXM1) and clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC). Zhonghua Zhong Liu Za Zhi 2011;33:426-30.  Back to cited text no. 6
    
7.
Xu N, Wu SD, Wang H, Wang Q, Bai CX. Involvement of FoxM1 in non-small cell lung cancer recurrence. Asian Pac J Cancer Prev 2012;13:4739-43.  Back to cited text no. 7
    
8.
Xu N, Jia D, Chen W, Wang H, Liu F, Ge H, et al. FoxM1 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor metastasis. PLoS One 2013;8:e59412.  Back to cited text no. 8
    
9.
Chen PM, Cheng YW, Wang YC, Wu TC, Chen CY, Lee H. Up-regulation of FOXM1 by E6 oncoprotein through the MZF1/NKX2-1 axis is required for human papillomavirus-associated tumorigenesis. Neoplasia 2014;16:961-71.  Back to cited text no. 9
    
10.
Kong FF, Qu ZQ, Yuan HH, Wang JY, Zhao M, Guo YH, et al. Overexpression of FOXM1 is associated with EMT and is a predictor of poor prognosis in non-small cell lung cancer. Oncol Rep 2014;31:2660-8.  Back to cited text no. 10
    
11.
Wang Y, Wen L, Zhao SH, Ai ZH, Guo JZ, Liu WC. FoxM1 expression is significantly associated with cisplatin-based chemotherapy resistance and poor prognosis in advanced non-small cell lung cancer patients. Lung Cancer 2013;79:173-9.  Back to cited text no. 11
    
12.
Kong FF, Zhu YL, Yuan HH, Wang JY, Zhao M, Gong XD, et al. FOXM1 regulated by ERK pathway mediates TGF-ß1-induced EMT in NSCLC. Oncol Res 2014;22:29-37.  Back to cited text no. 12
    
13.
Xu N, Zhang X, Wang X, Ge HY, Wang XY, Garfield D, et al. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells. Acta Pharmacol Sin 2012;33:675-81.  Back to cited text no. 13
    
14.
Gialmanidis IP, Bravou V, Amanetopoulou SG, Varakis J, Kourea H, Papadaki H. Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas. Lung Cancer 2009;66:64-74.  Back to cited text no. 14
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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