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.

• Authors: Eunhyang Park, Soo Young Park, Ping-Li Sun, Yan Jin, Ji Eun Kim, Sanghoon Jheon, Kwhanmien Kim, Choon Taek Lee, Hyojin Kim, Jin-Haeng Chung
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 27 Pg. 42502-42512 (Jul 05 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27285762 (Publication Type: Journal Article)

Chemical References

• AC133 Antigen
• CD44 protein, human
• Hyaluronan Receptors
• Isoenzymes
• NANOG protein, human
• Nanog Homeobox Protein
• Octamer Transcription Factor-3
• POU5F1 protein, human
• PROM1 protein, human
• SNAI1 protein, human
• SOX2 protein, human
• SOXB1 Transcription Factors
• Snail Family Transcription Factors
• Aldehyde Dehydrogenase 1 Family
• ALDH1A1 protein, human
• Retinal Dehydrogenase

Topics

• AC133 Antigen (metabolism)
• Adenocarcinoma (metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Aldehyde Dehydrogenase 1 Family
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Carcinoma, Squamous Cell (metabolism)
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hyaluronan Receptors (metabolism)
• Isoenzymes (metabolism)
• Lung Neoplasms (metabolism, pathology)
• Male
• Middle Aged
• Nanog Homeobox Protein (metabolism)
• Neoplastic Stem Cells (cytology)
• Octamer Transcription Factor-3 (metabolism)
• Prognosis
• Retinal Dehydrogenase (metabolism)
• Retrospective Studies
• SOXB1 Transcription Factors (metabolism)
• Snail Family Transcription Factors (metabolism)
• Young Adult