Abstract
Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma.
Highlights
The overall prognosis of lung cancer is poor
CD133, aldehyde dehydrogenase 1 (ALDH1) and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition
Our results showed that Cancer stem cells (CSCs) markers have distinct expression profiles in the two cancers
Summary
The overall prognosis of lung cancer is poor. According to the recently proposed cancer stem cell (CSC) theory, cancers are maintained by subpopulations of tumor cells that possess stem or progenitor cell-like characteristics. These cells exhibit pluripotency and self-renewal properties, and give rise to a heterogeneous population of tumor cells [1,2,3]. In non-small cell lung www.impactjournals.com/oncotarget cancer (NSCLC) cells, for example, CD133 and CD44 are CSC markers that confer drug resistance and stem cell-like properties [6,7,8,9]. The clinical impact of these markers is unclear, they may have a prognostic or predictive value in NSCLC
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