Integration of single-cell and spatial transcriptome sequencing identifies CDKN2A as a senescent biomarker in endothelial cells implicating hepatocellular carcinoma malignancy

Nov 6, 2024Journal of cancer research and clinical oncology

Combining single-cell and spatial gene analysis finds CDKN2A as a marker of aging in blood vessel cells linked to liver cancer severity

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Abstract

Senescent endothelial cells (ECs) in hepatocellular carcinoma (HCC) exhibit the most prominent senescent phenotype among various cell types within the tumor microenvironment.

  • Senescence-related genes (SRGs) show significant heterogeneity among different cell types in HCC.
  • Senescent ECs activate specific regulatory pathways through interactions with other cell types, potentially influencing tumor progression.
  • Spatial analysis indicates that senescent ECs are primarily located in the core region of HCC.
  • Interactions between senescent ECs and immune cells suggest their involvement in tumor progression and responses to immunotherapy.
  • CDKN2A is identified as an independent risk factor for poor prognosis in HCC, with higher risk associated with worse outcomes.
  • Senescent ECs defined by CDKN2A exhibit a secretory phenotype that promotes the proliferation and migration of HCC.

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Key numbers

CDKN2A
Independent risk factor for prognosis
Identified as a key senescence-related gene in HCC.
217 patients
Patient cohort size
Used for constructing the senescence-related prognostic model.

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