ArticleOncogene2014
ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
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- Distinct molecular subtypes of KRASClinical and translational medicine · 2025Article
- Unveiling prognostic factors and predictive modeling in lung adenocarcinoma with neuroendocrine differentiation.Translational cancer research · 2025Article
- Survival comparison of pulmonary neuroendocrine carcinoma, adenocarcinoma with neuroendocrine differentiation, and adenocarcinoma.Journal of thoracic disease · 2024Article
- Cobind: quantitative analysis of the genomic overlaps.Bioinformatics advances · 2023Article
- Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study.The Journal of pathology · 2022Article
- In-depth molecular analysis of combined and co-primary pulmonary large cell neuroendocrine carcinoma and adenocarcinoma.International journal of cancer · 2022Article
- Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting Rearranged during Transfection in Cancer: A Perspective on Small-Molecule Inhibitors and Their Clinical Development.Journal of medicinal chemistry · 2021Review
- Loss of cellular identity in common pre-clinical models of serine‑threonine kinase 11 (Liver kinase B1) loss.Cancer treatment and research communications · 2021Article
- Immunohistochemical Expression of Five Protein Combinations Revealed as Prognostic Markers in Asian Oral Cancer.Frontiers in genetics · 2021Article
- Targeting RET Kinase in Neuroendocrine Prostate Cancer.Molecular cancer research : MCR · 2020Article
- FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy.EBioMedicine · 2020Article
- Comparative analysis of TTF-1 binding DNA regions in small-cell lung cancer and non-small-cell lung cancer.Molecular oncology · 2020Article
- Characterization of cancer omics and drug perturbations in panels of lung cancer cells.Scientific reports · 2019Article
- Analysis of DLL3 and ASCL1 in Surgically Resected Small Cell Lung Cancer (HOT1702).The oncologist · 2019Article
- A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.Human pathology · 2019Article
- Molecular Links Between Angiogenesis and Neuroendocrine Phenotypes in Prostate Cancer Progression.Frontiers in oncology · 2019Review
- NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.Neuroendocrinology · 2019Article
- Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells.Cancers · 2018Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine (NE) cell development, but its value as a biomarker of NE differentiation in lung adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We examined ASCL1 expression in lung cancer samples of varied histologic subtype, clinical outcome and smoking status and compared with expression of traditional NE markers. ASCL1 mRNA expression was found almost exclusively in smokers with AD, in contrast to non-smokers and other lung cancer subtypes. ASCL1 protein expression by immunohistochemical (IHC) analysis correlated best with synaptophysin compared with chromogranin and CD56/NCAM. Analysis of a compendium of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas identified significantly higher expression levels of the RET oncogene in ASCL1-positive tumors (ASCL1(+)) compared with ASCL1(-) tumors (q-value <10(-9)). High levels of RET expression in ASCL1(+) but not in ASCL1(-) tumors was associated with significantly shorter overall survival (OS) in stage 1 (P=0.007) and in all AD (P=0.037). RET protein expression by IHC had an association with OS in the context of ASCL1 expression. In silico gene set analysis and in vitro experiments by ASCL1 shRNA in AD cells with high endogenous expression of ASCL1 and RET implicated ASCL1 as a potential upstream regulator of the RET oncogene. Also, silencing ASCL1 in AD cells markedly reduced cell growth and motility. These results suggest that ASCL1 and RET expression defines a clinically relevant subgroup of ∼10% of AD characterized by NE differentiation.
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