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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 4  |  Page : 800-803

Nestin is significantly associated with the overall survival of nonsmall cell lung cancer: A meta-analysis


Department of Thoracic Surgery, Jintan Hospital Affiliated to Jiangsu University, Jintan, Jiangsu, China

Date of Submission16-Oct-2016
Date of Decision04-Nov-2016
Date of Acceptance13-Nov-2016
Date of Web Publication21-Apr-2017

Correspondence Address:
Dehai Zhang
Department of Thoracic Surgery, Jintan Hospital Affiliated to Jiangsu University, No. 16 South Gate Street, Jintan 213200, Jiangsu
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.204901

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 > Abstract 


Aims: Some studies investigated the association between nestin and the overall survival (OS) of nonsmall cell lung cancer (NSCLC). However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between nestin and OS of NSCLC.
Materials and Methods: PubMed and EMBASE were searched to find relevant studies. The strength of the association was calculated with the hazard ratios (HRs) and respective 95% confidence intervals (CIs).
Results: High expression of nestin was significantly associated with OS of NSCLC (HR = 2.09; 95% CI = 1.59–2.77). In the stratified analysis by race, we found that the expression of nestin was significantly associated with OS of NSCLC in Asians (HR = 3.02; 95% CI = 1.80–5.07) and Caucasians (HR = 1.81; 95% CI = 1.21–2.71). In addition, when we limited the meta-analysis to studies that controlled for clinical parameters, a significant association between nestin and OS of NSCLC remained (HR = 2.19; 95% CI = 1.54–3.11). A sensitivity analysis showed no substantial modification of the estimates after exclusion of individual studies.
Conclusions: In conclusion, this meta-analysis suggested that high expression of nestin was significantly associated with OS of NSCLC.

Keywords: Nestin, nonsmall cell lung cancer, overall survival


How to cite this article:
Zhang D, Wang J. Nestin is significantly associated with the overall survival of nonsmall cell lung cancer: A meta-analysis. J Can Res Ther 2020;16:800-3

How to cite this URL:
Zhang D, Wang J. Nestin is significantly associated with the overall survival of nonsmall cell lung cancer: A meta-analysis. J Can Res Ther [serial online] 2020 [cited 2020 Sep 30];16:800-3. Available from: http://www.cancerjournal.net/text.asp?2020/16/4/800/204901




 > Introduction Top


Lung cancer is classified into two types according to biological characteristics: nonsmall cell lung cancer (NSCLC) and small cell lung cancer. NSCLC is hard to diagnose at early stage, and the 5-year overall survival (OS) is <15% for the patients with advanced tumor, node, metastasis stage.[1] Most of these patients die of the late occurrence of multiorgan metastases.

Nestin belongs to a Class VI intermediate filament protein originally found in neuroepithelial stem cells and neural cells.[2] Nestin regulates prostate cancer cell invasion,[3] epithelial-mesenchymal transition-related factors in pancreatic adenocarcinoma,[4] and drug resistance in other cancers.[5] Some studies investigated the association between nestin and the OS of NSCLC.[6],[7],[8],[9],[10],[11],[12] However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between nestin and the OS of NSCLC.


 > Materials and Methods Top


Publication search

PubMed and EMBASE were searched to find relevant studies. The search terms were “Nestin” and “NSCLC” or “nonsmall cell lung cancer.” There was no language restriction. Review articles and original papers were searched by hand for additional eligible studies.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) the diagnosis of NSCLC was confirmed by pathology; (2) an unrelated case–control study in which family members were excluded; (3) the study evaluate the association between nestin and the OS of NSCLC; (4) sufficient published data for estimating an hazard ratio (HR) with 95% confidence interval (CI). The exclusion criteria were as follows: (1) the NSCLC patients were not confirmed by pathology; (2) reviews or abstracts. When authors reported two or more publications on the same patient population, only the largest study was selected.

Data extraction

The following data were recorded from each article: first author, years of publication, race, study design, age, gender, stage of NSCLC, OS, duration of follow-up, numbers of cases, parameters for adjustment. The data were extracted by two of the authors independently. Discrepancies between these two authors were resolved by discussion. The included studies were assessed independently by the two reviewers using the Newcastle–Ottawa Scale.

Statistical analysis

The strength of the association between nestin and OS of NSCLC was calculated with the HR and 95% CIs. The significance of the pooled odds ratio (OR) was determined by the Z-test, and P < 0.05 was considered statistically significant. Statistical heterogeneity among studies was assessed with the I2 statistics. This value ranges from 0% (complete consistency) to 100% (complete inconsistency). If the I2 value was more than 50%, the random effects model was chosen to calculate the pooled OR; otherwise, the fixed effects model was used. In the sensitivity analysis, we did the meta-analysis in different study design to assess how conclusions might be affected. The presence of publication bias was assessed by a visual inspection of a funnel plot. All statistical tests were used by the Revman 5.1 software (Nordic Cochrane Centre, Copenhagen, Denmark) and STATA 11.0 software (StataCorp, College Station, TX, USA).


 > Results Top


Literature search

Ten articles on nestin and OS of NSCLC met the study inclusion criteria [Figure 1] and were included in the meta-analysis.[6],[7],[8],[9],[10],[11],[12] A total of seven studies with 817 NSCLC patients were included in this meta-analysis. Four studies were performed in Asians while three studies were conducted in Caucasians. Characteristics of studies investigating the association between nestin and OS of NSCLC are listed in [Table 1].
Figure 1: Studies selection

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Table 1: Characteristics of the included studies

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Meta-analysis

High expression of nestin was significantly associated with OS of NSCLC (HR = 2.09; 95% CI = 1.59–2.77) [Figure 2]. In the stratified analysis by race, we found that the expression of nestin was significantly associated with OS of NSCLC in Asians (HR = 3.02; 95% CI = 1.80–5.07) and Caucasians (HR = 1.81; 95% CI = 1.21–2.71). In addition, when we limited the meta-analysis to studies that controlled for clinical parameters, a significant association between nestin and OS of NSCLC remained (HR = 2.19; 95% CI = 1.54–3.11). A sensitivity analysis showed no substantial modification of the estimates after exclusion of individual studies (data not shown).
Figure 2: The association between the expression of nestin and overall survival of nonsmall cell lung cancer

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The shape of the funnel plot showed no obvious asymmetry [Figure 3]. Egger's test suggested that no publication bias was present (P = 0.75).
Figure 3: Funnel plot between the expression of nestin and overall survival of nonsmall cell lung cancer

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 > Discussion Top


The association between nestin and OS of NSCLC has been studied extensively. However, previous studies were contradictory. Therefore, we did this meta-analysis. High expression of nestin was significantly associated with OS of NSCLC. In the stratified analysis by race, we found that the expression of nestin was significantly associated with OS of NSCLC in Asians and Caucasians. In addition, when we limited the meta-analysis to studies that controlled for clinical parameters, a significant association between nestin and OS of NSCLC remained.

Nestin expression has been reported to be associated with the prognosis of many solid tumors. In a mouse model system, nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth.[13] Nestin knockdown enhanced chemotherapeutic efficacy in nude mice.[14] High nestin levels indicate poor prognosis in patients with Ewing sarcoma.[15] Nestin expression significantly correlated with overall tumor grade, lymph node, distant metastasis, and stage in epithelial ovarian cancer.[16] Lv et al. showed that nestin protein abundance was significantly correlated with the histological grade of glioma.[17]

Our meta-analysis had some limitations. First, the numbers of published studies were not sufficient for a comprehensive analysis, particularly for Africans. Second, we did not carry out meta-analysis on other clinical factors due to limited data. Third, as a meta-analysis of observational studies, it was prone to bias (e.g., recall and selection bias) inherent in the original studies.


 > Conclusions Top


This meta-analysis suggested that high expression of nestin was significantly associated with OS of NSCLC. Well-designed studies with larger sample size and more ethnic groups should be considered to further confirm this association.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Alberg AJ, Ford JG, Samet JM; American College of Chest Physicians. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132 3 Suppl: 29S-55S.  Back to cited text no. 1
    
2.
Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell 1990;60:585-95.  Back to cited text no. 2
    
3.
Hyder CL, Lazaro G, Pylvänäinen JW, Roberts MW, Qvarnström SM, Eriksson JE. Nestin regulates prostate cancer cell invasion by influencing the localisation and functions of FAK and integrins. J Cell Sci 2014;127(Pt 10):2161-73.  Back to cited text no. 3
    
4.
Hagio M, Matsuda Y, Suzuki T, Ishiwata T. Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines. Mol Clin Oncol 2013;1:83-7.  Back to cited text no. 4
    
5.
Tabata K, Matsumoto K, Minami S, Ishii D, Nishi M, Fujita T, et al. Nestin is an independent predictor of cancer-specific survival after radical cystectomy in patients with urothelial carcinoma of the bladder. PLoS One 2014;9:e91548.  Back to cited text no. 5
    
6.
Janikova M, Skarda J, Dziechciarkova M, Radova L, Chmelova J, Krejci V, et al. Identification of CD133+/nestin+putative cancer stem cells in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154:321-6.  Back to cited text no. 6
    
7.
Ryuge S, Sato Y, Jiang SX, Wang G, Matsumoto T, Katono K, et al. Prognostic impact of nestin expression in resected large cell neuroendocrine carcinoma of the lung. Lung Cancer 2012;77:415-20.  Back to cited text no. 7
    
8.
Skarda J, Kolar Z, Janikova M, Radova L, Kolek V, Fridman E, et al. Analysis of the prognostic impact of nestin expression in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156:135-42.  Back to cited text no. 8
    
9.
Ryuge S, Sato Y, Wang GQ, Matsumoto T, Jiang SX, Katono K, et al. Prognostic significance of nestin expression in resected non-small cell lung cancer. Chest 2011;139:862-9.  Back to cited text no. 9
    
10.
Chen Z, Wang J, Cai L, Zhong B, Luo H, Hao Y, et al. Role of the stem cell-associated intermediate filament nestin in malignant proliferation of non-small cell lung cancer. PLoS One 2014;9:e85584.  Back to cited text no. 10
    
11.
Sterlacci W, Savic S, Fiegl M, Obermann E, Tzankov A. Putative stem cell markers in non-small-cell lung cancer: A clinicopathologic characterization. J Thorac Oncol 2014;9:41-9.  Back to cited text no. 11
    
12.
Narita K, Matsuda Y, Seike M, Naito Z, Gemma A, Ishiwata T. Nestin regulates proliferation, migration, invasion and stemness of lung adenocarcinoma. Int J Oncol 2014;44:1118-30.  Back to cited text no. 12
    
13.
Li P, Lee EH, Du F, Gordon RE, Yuelling LW, Liu Y, et al. Nestin mediates hedgehog pathway tumorigenesis. Cancer Res 2016;76:5573-83.  Back to cited text no. 13
    
14.
Zhang Y, Zeng S, Ma J, Deng G, Qu Y, Guo C, et al. Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance. J Exp Clin Cancer Res 2016;35:111.  Back to cited text no. 14
    
15.
Zambo I, Hermanova M, Zapletalova D, Skoda J, Mudry P, Kyr M, et al. Expression of nestin, CD133 and ABCG2 in relation to the clinical outcome in pediatric sarcomas. Cancer Biomark 2016;17:107-16.  Back to cited text no. 15
    
16.
Osman WM, Shash LS, Ahmed NS. Emerging role of nestin as an angiogenesis and cancer stem cell marker in epithelial ovarian cancer: Immunohistochemical study. Appl Immunohistochem Mol Morphol 2016. [Epub ahead of print].  Back to cited text no. 16
    
17.
Lv D, Lu L, Hu Z, Fei Z, Liu M, Wei L, et al. Nestin expression is associated with poor clinicopathological features and prognosis in glioma patients: An association study and meta-analysis. Mol Neurobiol 2016. [Epub ahead of print].  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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