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

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

Abstract 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 type...

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Main Authors: Bhavneet Bhinder, Verena Friedl, Sunantha Sethuraman, Davide Risso, Kami E. Chiotti, R. Jay Mashl, Kyle P. Ellrott, Jordan A. Lee, Christopher K. Wong, Kofi Gyan, Aditya Deshpande, Marcin Imielinski, Rohan Bareja, Josh Stuart, Myron Peto, Katherine A. Hoadley, Alexander J. Lazar, Andrew D. Cherniack, Jingchun Zhu, Shaolong Cao, Mark Rubin, Wenyi Wang, Oliver F. Bathe, Nicolas Robine, Li Ding, Peter W. Laird, Wanding Zhou, Hui Shen, Vésteinn Thorsson, Jen Jen Yeh, Matthew H. Bailey, Daniel Cui Zhou, Xianlu L. Peng, Mary Goldman, Yongsheng Li, Anil Korkut, Nidhi Sahni, D. Neil Hayes, Michael K. A. Mensah, Ina Felau, Anab Kemal, Samantha Caesar-Johnson, John A. Demchok, Liming Yang, Martin L. Ferguson, Roy Tarnuzzer, Zhining Wang, Jean C. Zenklusen, The Cancer Genome Atlas Analysis Network, Paul Spellman, Olivier Elemento
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Tumor microenvironment
iScores
Integrated scores
Cell type estimation
Deconvolution
Pan-cancer analysis
Online Access:https://doi.org/10.1038/s41598-025-09075-y
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Summary:Abstract 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).
ISSN:2045-2322

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