Pan-cancer immune and stromal deconvolution predicts clinical outcomes and mutation profiles.

Publication date: Jul 04, 2025

Traditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better survival in bladder cancer for luminal and basal squamous subtypes, as well as in melanoma for RAS-hotspot subtypes. Our detailed deconvolution and mutational correlation analyses uncover 35 therapeutic target and candidate response biomarkers hypotheses (including CASP8 and RAS pathway genes).

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Concepts Keywords
Biomarkers Biomarkers, Tumor
Cancer Biomarkers, Tumor
Infiltration Cell type estimation
Rich Deconvolution
Gene Expression Profiling
Humans
Immune cells
Integrated scores
iScores
Mutation
Neoplasms
Pan-cancer analysis
Prognosis
Somatic mutations
Stroma
Stromal Cells
Survival
Tumor Microenvironment
Tumor microenvironment
Tumor progression

Semantics

Type Source Name
disease MESH cancer
drug DRUGBANK Tropicamide
disease MESH bladder cancer
pathway KEGG Bladder cancer
drug DRUGBANK Phenobarbital
disease MESH melanoma
pathway KEGG Melanoma
drug DRUGBANK Rasagiline
drug DRUGBANK Ademetionine
drug DRUGBANK Coenzyme M
disease MESH Carcinogenesis
disease MESH metastasis
drug DRUGBANK Gold
disease MESH hypoxia
pathway REACTOME Methylation

Original Article

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