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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

ABSTRACT: A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

PROVIDER: PRJNA634310 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11825068_1.fastq.gz	Fastqsanger.gz
	SRR11825068_2.fastq.gz	Fastqsanger.gz
	SRR11825069_1.fastq.gz	Fastqsanger.gz
	SRR11825069_2.fastq.gz	Fastqsanger.gz
	SRR11825070_1.fastq.gz	Fastqsanger.gz

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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [tumor]

Project description:A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [tumor]

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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [cell lines]

Project description:A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [cell lines]

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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks.

Project description:BackgroundLung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression.ResultsA high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD.ConclusionsOur study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.

| S-EPMC8127276 | biostudies-literature

Molecular subclasses of high-grade glioma: prognosis, disease progression, and neurogenesis

Project description:Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006. Keywords: Disease state comparison

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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-22 | GSE150977 | GEO

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [tumor]

Project description:Lung adenocarcinoma (LUAD) is a high malignant tumor mostly occurs in adult patients, which is also a highly heterogeneous disease that involved multi different alterations. Some alterations such like EGFR mutations are frequently observed in LUAD patients, but the mechanisms that drive LUAD tumorigenesis and progression remain largely unclear, which need further researches. For example, epigenetic processes play important roles in cancers, but the variations in the enhancer and super enhancer landscapes of LUAD patients have rarely been studied. Here, to provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of the tumor and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression.

2020-05-22 | GSE150976 | GEO

Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses

Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis

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A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks [cell lines]

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Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses [methylation]

Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here we combined single-cell multi-omics, transcriptomics and methylomics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the phenotypic traits of the subclasses, and the study of additional unstratified KC entities uncovered distinct clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis.

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Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses [Multiome]

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