Abstract
CD133 has been identified as a potential cancer stem cell (CSC) marker in non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of CD133 in NSCLC remains controversial. In this study, a meta-analysis with a total number of 13 studies was performed to clarify the association between CD133 expression and clinical outcomes in publications up to June 2013. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to assess the association between CD133 expression and the clinicopathological characteristics of NSCLC. Hazard ratios (HRs) and their 95 % CI were used to quantify the predictive ability of CD133 on NSCLC prognosis. Analysis of these data showed that CD133 expression was not associated with any clinicopathological parameters except for histology (pooled OR = 1.35, 95%CI = 1.04–1.76, P = 0.024) and tumor differentiation (pooled OR = 3.19, 95%CI = 1.10–9.21, P = 0.032). Simultaneously, we also found that positive CD133 expression was not associated with disease-free survival (DFS) (pooled HR = 1.76, 95 % CI = 0.87–3.57, P = 0.114, random-effect) but was associated with overall survival (OS) (pooled HR = 2.06, 95 % CI = 1.08–3.91, P = 0.027, random-effect). Overall, it is appropriate to regard CD133 expression as a potential prognostic factor for the OS of NSCLC patients.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Esposito L, Conti D, Ailavajhala R, Khalil N, Giordano A. Lung cancer: are we up to the challenge? Curr Genomics. 2010;11:513–8.
Alberg AJ, Ford JG, Samet JM. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:29S–55.
Dontu G, Liu S, Wicha MS. Stem cells in mammary development and carcinogenesis: implications for prevention and treatment. Stem Cell Rev. 2005;1:207–13.
Ribatti D. Cancer stem cells and tumor angiogenesis. Cancer Lett. 2012;321:13–7.
Baccelli I, Trumpp A. The evolving concept of cancer and metastasis stem cells. J Cell Biol. 2012;198:281–93.
Perona R, Lopez-Ayllon BD, de Castro Carpeno J, Belda-Iniesta C. A role for cancer stem cells in drug resistance and metastasis in non-small-cell lung cancer. Clin Transl Oncol. 2011;13:289–93.
Kitamura H, Okudela K, Yazawa T, Sato H, Shimoyamada H. Cancer stem cell: implications in cancer biology and therapy with special reference to lung cancer. Lung Cancer. 2009;66:275–81.
Salnikov AV, Gladkich J, Moldenhauer G, Volm M, Mattern J, Herr I. Cd133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients. Int J Cancer J Int Cancer. 2010;126:950–8.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.
Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15:504–14.
Arne G, Kristiansson E, Nerman O, Kindblom LG, Ahlman H, Nilsson B, et al. Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location and poor prognosis. Int J Cancer J Int Cancer. 2011;129:1149–61.
Boegl M, Prinz C. Cd133 expression in different stages of gastric adenocarcinoma. Br J Cancer. 2009;100:1365–6. author reply 1367.
Wu S, Yu L, Wang D, Zhou L, Cheng Z, Chai D, et al. Aberrant expression of CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry. BMC Cancer. 2012;12:535.
Woo T, Okudela K, Mitsui H, Yazawa T, Ogawa N, Tajiri M, et al. Prognostic value of CD133 expression in stage i lung adenocarcinomas. Int J Clin Exp Pathol. 2010;4:32–42.
Mizugaki H, Sakakibara-Konishi J, Kikuchi J, Moriya J, Hatanaka KC, Kikuchi E, Kinoshita I, Oizumi S, Dosaka-Akita H, Matsuno Y, Nishimura M. Cd133 expression: A potential prognostic marker for non-small cell lung cancers. Int J Clin Oncol. 2013.
Sullivan JP, Spinola M, Dodge M, Raso MG, Behrens C, Gao B, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res. 2010;70:9937–48.
Yang X, Takano Y, Zheng HC. The pathobiological features of gastrointestinal cancers (review). Oncol Lett. 2012;3:961–9.
Liu L, Wu C, Wang Y, Zhong R, Duan S, Wei S, et al. Combined effect of genetic polymorphisms in p53, p73, and mdm2 on non-small cell lung cancer survival. J Thorac Oncol. 2011;6:1793–800.
Liu L, Yuan P, Wu C, Zhang X, Wang F, Guo H, et al. Assessment of XPD Lys751gln and XRCC1 t-77c polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer. 2011;73:110–5.
Chen S, Song X, Chen Z, Li X, Li M, Liu H, et al. CD133 expression and the prognosis of colorectal cancer: a systematic review and meta-analysis. PLoS One. 2013;8:e56380.
Wen L, Chen XZ, Yang K, Chen ZX, Zhang B, Chen JP, et al. Prognostic value of cancer stem cell marker cd133 expression in gastric cancer: a systematic review. PLoS One. 2013;8:e59154.
Liu YP, Yang CJ, Huang MS, Yeh CT, Wu AT, Lee YC, et al. Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by activating notch signaling. Cancer Res. 2013;73:406–16.
Lundin A, Driscoll B. Lung cancer stem cells: Progress and prospects. Cancer Lett. 2012.
Okudela K, Woo T, Mitsui H, Tajiri M, Masuda M, Ohashi K. Expression of the potential cancer stem cell markers, CD133, CD44, ALDH1, and beta-catenin, in primary lung adenocarcinoma-their prognostic significance. Pathol Int. 2012;62:792–801.
Xu YH, Zhang GB, Wang JM, Hu HC. B7-H3 and CD133 expression in non-small cell lung cancer and correlation with clinicopathologic factors and prognosis. Saudi Med J. 2010;31:980–6.
Acknowledgments
Research supported by National Natural Science Foundation of China (#81370078, #30930080, #81161120537, and #81001231), malignant tumor biomarkers in Jiangsu Province Key Laboratory (#11ZLKF09), the Natural Science Foundation of Jiangsu Province (#BK2012840), the Postdoctoral Science Foundation of China (#20100481165), Undergraduates Practice and InnovationTraining Project of Jiangsu Higher Education Institutes (#2012JSSPITP1021), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding authors
Additional information
Weimin Wang, Yansu Chen, and Jianliang Deng contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wang, W., Chen, Y., Deng, J. et al. The prognostic value of CD133 expression in non-small cell lung cancer: a meta-analysis. Tumor Biol. 35, 9769–9775 (2014). https://doi.org/10.1007/s13277-014-2270-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-014-2270-9