E-cadherin as a Prognostic Factor in Stage I Non-Small Cell Lung Cancer: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 CHENBao-qing , YANGHui , HUBin-bin , XUEJian-xin ,  LUYou

Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LUYou, Email: radyoulu@hotmail.com

Keywords：

E-cadherin; Epithelial-mesenchymal transition; Non-small cell lung cancer; Prognosis; Meta-analysis; Cohort study

DOI：

10.7507/1672-2531.20160081

Video：

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Objective To systematically review the prognostic value of E-cadherin expression in stage I non-small cell lung cancer (NSCLC). Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015), CNKI, CBM and WanFang Data were searched to collect cohort studies about the prognostic value of E-cadherin expression in stage I NSCLC from inception to Jun. 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results A total of 9 cohort studies, involving 1028 patients were included. The results of meta-analysis showed that, the lower E-cadherin expression group had a lower overall survival rate than that of the higher E-cadherin expression group (HR=1.74, 95%CI 1.36 to 2.24, P＜0.00001). However, there was no significant difference between two groups in disease free survival (HR=2.08, 95%CI 0.8 to 5.40, P=0.13). Subgroup analysis showed that, the lower E-cadherin expression group had a worse overall survival when groups were divided by different cut-off values, E-cadherin location site or different nations (all value P＜0.05). Conclusion Current evidence shows that, reduced E-cadherin expression could predict poor prognostic outcome in patients with stage I NSCLC. Due to the limited quantity and quality of included studies, the above conclusions need to be verified by more high quality studies.

Citation： CHENBao-qing, YANGHui, HUBin-bin, XUEJian-xin, LUYou. E-cadherin as a Prognostic Factor in Stage I Non-Small Cell Lung Cancer: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(5): 517-522. doi: 10.7507/1672-2531.20160081 Copy

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14.	Zvrko E, Mikic A, Jancic S. Relationship of E-cadherin with cervical lymph node metastasis in laryngeal cancer. Coll Antropol, 2012, 36(Suppl): 2119-2124.
15.	Uchikado Y, Okumura H, Ishigami S, et al. Increased Slug and decreased E-cadherin expression is related to poor prognosis in patients with gastric cancer. Gastric Cancer, 2011, 14(1): 41-49.
16.	Tian X, Liu Z, Niu B, et al. E-cadherin/beta-catenin complex and the epithelial barrier. J Biomed Biotechnol, 2011, 2011567305.
17.	He X, Chen Z, Jia M, et al. Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One, 2013, 8(7): e70858.
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19.	Xu XL, Ling ZQ, Chen SZ, et al. The impact of E-cadherin expression on the prognosis of esophageal cancer: a meta-analysis. Dis Esophagus, 2014, 27(1): 79-86.
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21.	Vessey CJ, Wilding J, Folarin N, et al. Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. J Pathol, 1995, 176(2): 151-159.
22.	Hicks K, Wong C. Identifying lung cancer patients who may be eligible for epidermal growth factor receptor (EGFR) mutation testing. N Z Med J, 2013, 126(1381): 49-56.
23.	Yang YL, Chen MW, Xian L. Prognostic and clinicopathological significance of downregulated E-cadherin expression in patients with non-small cell lung cancer (NSCLC): a meta-analysis. PLoS One, 2014, 9(6): e99763.
24.	Barr S, Thomson S, Buck E, et al. Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin Exp Metastasis, 2008, 25(6): 685-693.

1. Nurwidya F, Takahashi F, Murakami A, et al. Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat, 2012, 44(3): 151-156.
2. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
3. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med, 1998, 17(24): 2815-2834.
4. Cho S, Sung SW, Jheon S, et al. Risk of recurrence in surgically resected stage I adenocarcinoma of the lung: histopathologic and immunohistochemical analysis. Lung, 2008, 186(6): 411-419.
5. Ono K, Uramoto H, Hanagiri T. Expression of dysadherin and cytokeratin as prognostic indicators of disease-free survival in patients with stage I NSCLC. Anticancer Res, 2010, 30(9): 3273-3278.
6. Ono S, Ishii G, Nagai K, et al. Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. Chest, 2013.143(4): 963-970.
7. Huang C, Liu D, Masuya D, et al. Clinical application of biological markers for treatments of resectable non-small-cell lung cancers. Br J Cancer, 2005, 92(7): 1231-1239.
8. Lin Q, Li M, Shen ZY, et al. Prognostic impact of vascular endothelial growth factor-A and E-cadherin expression in completely resected pathologic stage I non-small cell lung cancer. Jpn J Clin Oncol, 2010, 40(7): 670-676.
9. Hirata T, Fukuse T, Naiki H, et al. Expression of E-cadherin and lymph node metastasis in resected non-small-cell lung cancer. Clin Lung Cancer, 2001, 3(2): 134-140.
10. Yamashita T, Uramoto H, Onitsuka T, et al. Association between lymphangiogenesis-/micrometastasis-and adhesion-related molecules in resected stage I NSCLC. Lung Cancer, 2010, 70(3): 320-328.
11. Zhu ZH, Sun BY, Ma Y, et al. Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer. J Clin Oncol, 2009, 27(7): 1091-1099.
12. 谢泽明, 朱志华, 张兰军, 等. I期非小细胞肺癌中侵袭与转移相关蛋白的表达及其预后意义. 第四军医大学学报, 2008, 29(8): 743-745.
13. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest, 2009, 119(6): 1420-1428.
14. Zvrko E, Mikic A, Jancic S. Relationship of E-cadherin with cervical lymph node metastasis in laryngeal cancer. Coll Antropol, 2012, 36(Suppl): 2119-2124.
15. Uchikado Y, Okumura H, Ishigami S, et al. Increased Slug and decreased E-cadherin expression is related to poor prognosis in patients with gastric cancer. Gastric Cancer, 2011, 14(1): 41-49.
16. Tian X, Liu Z, Niu B, et al. E-cadherin/beta-catenin complex and the epithelial barrier. J Biomed Biotechnol, 2011, 2011567305.
17. He X, Chen Z, Jia M, et al. Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One, 2013, 8(7): e70858.
18. Keune WJ, Sims AH, Jones DR, et al. Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression. Cancer Res, 2013, 73(23): 6913-6925.
19. Xu XL, Ling ZQ, Chen SZ, et al. The impact of E-cadherin expression on the prognosis of esophageal cancer: a meta-analysis. Dis Esophagus, 2014, 27(1): 79-86.
20. Kase S, Sugio K, Yamazaki K, et al. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res, 2000, 6(12): 4789-4796.
21. Vessey CJ, Wilding J, Folarin N, et al. Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. J Pathol, 1995, 176(2): 151-159.
22. Hicks K, Wong C. Identifying lung cancer patients who may be eligible for epidermal growth factor receptor (EGFR) mutation testing. N Z Med J, 2013, 126(1381): 49-56.
23. Yang YL, Chen MW, Xian L. Prognostic and clinicopathological significance of downregulated E-cadherin expression in patients with non-small cell lung cancer (NSCLC): a meta-analysis. PLoS One, 2014, 9(6): e99763.
24. Barr S, Thomson S, Buck E, et al. Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin Exp Metastasis, 2008, 25(6): 685-693.

Chinese Journal of Evidence-Based Medicine

E-cadherin as a Prognostic Factor in Stage I Non-Small Cell Lung Cancer: A Meta-analysis

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