Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma

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.

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

“…CD133, a glycoprotein known as Prominin 1 (PROM1), has been considered as a CSC marker in various solid tumors 43-46. It has been reported that CD133 expression correlates significantly with TNBC subtype 30, 47.…”

A Novel Role For Nanog As An Early Cancer Risk Marker In Patients With Laryngeal Precancerous Lesions

“…Furthermore, NANOG has been found frequently aberrantly expressed in a variety of human cancers, including head and neck squamous cell carcinomas (HNSCC) 6 , 7 . NANOG expression in cancer has been associated with chemoresistance 8 , 9 , epithelial to mesenchymal transition (EMT) 6 and poor clinical outcome 7 , 10 – 12 .…”

Differences of tumor microenvironment between stage I lepidic-positive and lepidic-negative lung adenocarcinomas

“…CD44 expression is reportedly correlated with long survival and predominantly lepidic subtypes in lung adenocarcinoma, consistent, in part, with our results. 28 In fact, one of the supportive explanations is that the interaction between CD44 and its ligand of hyaluronic acid may inhibit angiogenesis and progression of cancers. 29 The current World Health Organization classification scheme proposes that the new adenocarcinoma in situ and minimally invasive carcinoma categories represent a stepwise progression of Lepþ adenocarcinoma.…”