An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas

Miyashita, Naoya; Horie, Masafumi; Suzuki, Hiroshi; Yoshihara, Masahito; Djureinovic, Dijana; Persson, Johannes; Brunnström, Hans; Lindskog, Cecilia; Elfving, Hedvig; Micke, Patrick; Saito, Akira; Nagase, Takahide

doi:10.1016/j.jtho.2018.07.096

Cited by 22 publications

(21 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistently, our genome‐wide analysis of SCLC cells revealed that TTF‐1 binding regions and TTF‐1‐regulated genes are associated with cellular differentiation and neural development. Of note, LADC that expresses ASCL1 shows neuroendocrine phenotype (Miyashita et al , ). Other reports indicate that LADC transforms into SCLC during the course of clinical treatments (Ferrer et al , ; Marcoux et al , ).…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of TTF‐1 binding DNA regions in small‐cell lung cancer and non‐small‐cell lung cancer

et al. 2019

View full text Add to dashboard Cite

Thyroid transcription factor-1 (TTF-1, encoded by the NKX2-1 gene) is highly expressed in small-cell lung carcinoma (SCLC) and lung adenocarcinoma (LADC), but how its functional roles differ between SCLC and LADC remains to be elucidated. Here, we compared the genome-wide distributions of TTF-1 binding regions and the transcriptional programs regulated by TTF-1 between NCI-H209 (H209), a human SCLC cell line, and NCI-H441 (H441), a human LADC cell line, using chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq). TTF-1 binding regions in H209 and H441 cells differed by 75.0% and E-box motifs were highly enriched exclusively in the TTF-1 binding regions of H209 cells. Transcriptome profiling revealed that TTF-1 is involved in neuroendocrine differentiation in H209 cells. We report that TTF-1 and achaete-scute homolog 1 (ASCL1, also known as ASH1, an E-box binding basic helix-loop-helix transcription factor, and a lineage-survival oncogene of SCLC) are coexpressed and bound to adjacent sites on target genes expressed in SCLC, and cooperatively regulate transcription. Furthermore, TTF-1 regulated expression of the Bcl-2 gene family and showed antiapoptotic function in SCLC. Our findings suggest that TTF-1 promotes SCLC growth and contributes to neuroendocrine and antiapoptotic gene expression by partly coordinating with ASCL1.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative analysis of TTF‐1 binding DNA regions in small‐cell lung cancer and non‐small‐cell lung cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Transcriptome and methylation profiles of lung cancer in IPF patients also remain to be elucidated. Recent studies have suggested that lung cancers of each histological subtype can be further subclassified based on gene expression and methylation patterns, which is related to different responses to cytotoxic agents, molecular targeted therapies, and immune checkpoint inhibitors [ 102 , 103 ]. Given that the mutation burden of lung cancer complicated with IPF is relatively high, as suggested by a recent report [ 62 ], immune checkpoint inhibitors might be beneficial.…”

Section: Clinical Implications and Future Perspectivesmentioning

confidence: 99%

The Role of TGF-β Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis

Saito

Horie

Micke

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and dismal prognosis. IPF patients are known to have an increased risk of lung cancer and careful decision-making is required for the treatment of lung cancer associated with IPF. Transforming growth factor (TGF)-β signaling plays a central role in tissue fibrosis and tumorigenesis. TGF-β-mediated pathological changes that occur in IPF lung tissue may promote the process of field cancerization and provide the microenvironment favorable to cancer initiation and progression. This review summarizes the current knowledge related to IPF pathogenesis and explores the molecular mechanisms that underlie the occurrence of lung cancer in the background of IPF, with an emphasis on the multifaceted effects of TGF-β signaling.

show abstract

“…Integrated analysis of methylation and gene expression for diagnosis, treatment, or prognosis has been reported in breast cancer, lung cancer, thyroid cancer, and hepatocellular carcinoma, head and neck squamous cell carcinoma, and polycystic ovary syndrome. 11 , 12 , 13 , 14 , 15 , 16 Although CC screening programs are now carried out worldwide, many women are still diagnosed with advanced CC which the overall prognosis remains poor. To date, only a limited number of reports about biomarkers were identified in CC by multi‐omics integrated analysis.…”

Section: Introductionmentioning

confidence: 99%

An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome

Han

Guan

et al. 2021

Clinical & Translational Med

View full text Add to dashboard Cite

show abstract

An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas

Abstract: These results suggest that ASCL1 defines a subgroup of lung adenocarcinoma with distinct molecular features by driving super-enhancer-mediated transcriptional programs.

Cited by 22 publications

References 51 publications

Comparative analysis of TTF‐1 binding DNA regions in small‐cell lung cancer and non‐small‐cell lung cancer

Comparative analysis of TTF‐1 binding DNA regions in small‐cell lung cancer and non‐small‐cell lung cancer

The Role of TGF-β Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis

An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome

Contact Info

Product

Resources

About