Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature

Activation of cellular hypoxia pathways, orchestrated by HIF (hypoxia-inducible factor) transcription factors, is a common feature of multiple tumor types, resulting from microenvironment factors and oncogenic mutation. Although they help drive many of the “hallmarks” of cancer and are associated wi...

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Main Authors: Lombardi, O, Li, R, Halim, S, Choudhry, H, Ratcliffe, PJ, Mole, DR
Format: Journal article
Language:English
Published: Elsevier 2022
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author Lombardi, O
Li, R
Halim, S
Choudhry, H
Ratcliffe, PJ
Mole, DR
author_facet Lombardi, O
Li, R
Halim, S
Choudhry, H
Ratcliffe, PJ
Mole, DR
author_sort Lombardi, O
collection OXFORD
description Activation of cellular hypoxia pathways, orchestrated by HIF (hypoxia-inducible factor) transcription factors, is a common feature of multiple tumor types, resulting from microenvironment factors and oncogenic mutation. Although they help drive many of the “hallmarks” of cancer and are associated with poor outcome and resistance to therapy, the transcriptional targets of HIF vary considerably depending on the cell type. By integrating 72 genome-wide assays of HIF binding and transcriptional regulation from multiple cancer types, we define a consensus set of 48 HIF target genes that is highly conserved across cancer types and cell lineages. These genes provide an effective marker of HIF activation in bulk and single-cell transcriptomic analyses across a wide range of cancer types and in malignant and stromal cell types. This allows the tissue-orchestrated responses to the hypoxic tumor microenvironment and to oncogenic HIF activation to be deconvoluted at the tumor and single-cell level.
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spelling oxford-uuid:d19f6882-38af-427f-8a9a-29a0057bf6dc2023-01-20T15:33:43ZPan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signatureJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d19f6882-38af-427f-8a9a-29a0057bf6dcEnglishSymplectic ElementsElsevier2022Lombardi, OLi, RHalim, SChoudhry, HRatcliffe, PJMole, DRActivation of cellular hypoxia pathways, orchestrated by HIF (hypoxia-inducible factor) transcription factors, is a common feature of multiple tumor types, resulting from microenvironment factors and oncogenic mutation. Although they help drive many of the “hallmarks” of cancer and are associated with poor outcome and resistance to therapy, the transcriptional targets of HIF vary considerably depending on the cell type. By integrating 72 genome-wide assays of HIF binding and transcriptional regulation from multiple cancer types, we define a consensus set of 48 HIF target genes that is highly conserved across cancer types and cell lineages. These genes provide an effective marker of HIF activation in bulk and single-cell transcriptomic analyses across a wide range of cancer types and in malignant and stromal cell types. This allows the tissue-orchestrated responses to the hypoxic tumor microenvironment and to oncogenic HIF activation to be deconvoluted at the tumor and single-cell level.
spellingShingle Lombardi, O
Li, R
Halim, S
Choudhry, H
Ratcliffe, PJ
Mole, DR
Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title_full Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title_fullStr Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title_full_unstemmed Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title_short Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature
title_sort pan cancer analysis of tissue and single cell hif pathway activation using a conserved gene signature
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