关键词: ALDH1 CD44 Epithelial–mesenchymal transition NANOG Non-small cell lung cancer

Mesh : Adenocarcinoma of Lung / enzymology genetics pathology Adult Aged Aged, 80 and over Aldehyde Dehydrogenase 1 Family Biomarkers, Tumor / biosynthesis genetics Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic Humans Hyaluronan Receptors / biosynthesis Immunohistochemistry Isoenzymes / biosynthesis genetics Lung Neoplasms / enzymology genetics pathology Male Middle Aged Nanog Homeobox Protein / biosynthesis Neoplastic Stem Cells / enzymology pathology Prognosis RNA, Messenger / biosynthesis genetics Retinal Dehydrogenase / biosynthesis genetics

来  源:   DOI:10.1007/s00432-019-02906-2   PDF(Sci-hub)

Abstract:
OBJECTIVE: Cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) pathways are crucial for cancer progression. However, synergistic interactions between CSC and EMT are not clear in non-small cell lung cancer (NSCLC). The objective of this study was to investigate CSC markers such as CD44, NANOG, and ALDH1 expression and its correlation with EMT markers in NSCLC patients. Its association with survival was also determined.
METHODS: CD44, NANOG, and ALDH1 protein expression was evaluated in 267 resected NSCLC and its correlation with e-cadherin, β-catenin, p120 catenin, vimentin, SNAIL, and TWIST expressions was determined based on immunohistochemical and mRNA expression data from The Cancer Genome Atlas (TCGA) database. Survival analyses also were performed based on immunohistochemistry and mRNA expression data from Gene Expression Omnibus dataset.
RESULTS: ALDH1 expression in lung adenocarcinoma was positively correlated with the epithelial-like phenotype, low vimentin and low TWIST in immunohistochemical and mRNA expression data. NANOG and ALDH1 expressions measured by immunohistochemical and mRNA expression profiling data of adenocarcinomas were associated with a favorable prognosis. ALDH1 was an independent favorable prognostic marker for overall survival or recurrence-free survival in adenocarcinoma (P = 0.026 and P = 0.033, respectively). The epithelial-like phenotype expressing P120-catenin and beta-catenin was associated with a favorable prognosis; however, the TWIST-expressing mesenchymal-like phenotype was correlated with an unfavorable prognosis.
CONCLUSIONS: NANOG and ALDH1 protein or mRNA expression showed improved prognosis in adenocarcinoma alone. ALDH1 expression correlated with an epithelial-like phenotype.
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