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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.

SUBMITTER: Park E

PROVIDER: S-EPMC5173151 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Park Eunhyang E Park Soo Young SY Sun Ping-Li PL Jin Yan Y Kim Ji Eun JE Jheon Sanghoon S Kim Kwhanmien K Lee Choon Taek CT Kim Hyojin H Chung Jin-Haeng JH

Oncotarget 20160701 27

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 bind ...[more]

PMID: 27285762

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Project description:BackgroundNumerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD.MethodsThe data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.ResultsOverall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment.ConclusionsThe key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

Project description:Cuproptosis is a novel and unique cell death mode that has attracted significant interest in recent years. Little is currently known about whether cuproptosis-related genes (CRGs) are associated with the pathophysiology and survival of patients with lung adenocarcinoma (LUAD). The present study sought to characterize the transcriptional and genetic alteration of CRGs in LUAD and its potential significance in the tumor microenvironment and predicting the prognosis of LUAD. The secondary eventual aim was to study the role of CRGs in predicting immunotherapy response and its clinical value combined with the TNM stage. We found that several CRGs, including FDX1, DLD, SLC31A1, and MTF1, were enriched in macrophages in our single-cell RNA-seq data. Three distinct molecular subtypes were identified and correlated with clinicopathological characteristics, prognosis, biological pathways, and tumor microenvironment (TME) in LUAD. We developed a cuproptosis-related gene score (CRG_score) and validated it in three independent cohorts and clinical subtypes. The low CRG_score group, characterized by a greater immune score, immunophenoscore (IPS), lower tumor immune dysfunction and exclusion (TIDE) score, and T-cell dysfunction score, had a better prognosis, suggesting that the low CRG_score group responded more favorably to immunotherapy, which was validated in the anti-PD-1/L1 immunotherapy cohort (IMvigor210). In contrast, the high CRG_score group was more sensitive to targeted therapy and chemotherapy, with a higher cancer stem cell (CSC) index and lower half-maximal inhibitory concentration (IC50) for many drugs. Given the established crosstalk between CRG_score and tumor TNM stage, we developed an accurate nomogram for clinical application of the CRG_score. Taken together, our rigorous and comprehensive examination of CRGs in LUAD identified their potential functions in TME, clinicopathological characteristics, drug sensitivity, and prognosis. These findings improve the current understanding of cuproptosis in LUAD, paving the way for more accurate prognosis assessment and tailored treatment for this patient population.

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Dataset Information

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

Publications

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

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