Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma.
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.
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
Eunhyang
E
Park
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Soo Young
SY
Park
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Department of Pathology, Jilin University Second Hospital, Changchun, China.
Ping-Li
PL
Sun
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Yan
Y
Jin
Department of Pathology, Seoul National University Boramae Hospital, Seoul, Republic of Korea.
Ji Eun
JE
Kim
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Sanghoon
S
Jheon
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Kwhanmien
K
Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Choon Taek
CT
Lee
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Hyojin
H
Kim
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Jin-Haeng
JH
Chung
D000071916:AC133 Antigen / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D055815:Young Adult
D000071916:AC133 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; C000604407:SNAI1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000071250:Snail Family Transcription Factors; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
adenocarcinoma; cancer stem cell marker; immunohistochemistry; lung cancer; Nanog