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

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-07-04 DOI:10.1038/s41598-025-09075-y

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, Paul Spellman, Olivier Elemento

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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).

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泛癌免疫和间质反褶积预测临床结果和突变谱。

传统的基因表达反卷积方法只能评估有限数量的细胞类型，因此不能捕捉肿瘤微环境（TME）的全部复杂性。在这里，我们整合了9种反卷积工具来评估33种不同癌症类型的10,592个肿瘤中的79种TME细胞类型，创建了最全面的TME分析。总的来说，我们发现了41种免疫浸润模式和基质谱，确定了每种癌症的异质性但独特的TME谱和一些新的发现。我们的研究结果表明，白细胞在区分各种肿瘤类型中发挥着重要作用，并且共享的免疫丰富的TME集群预测膀胱癌的管腔和基底鳞状亚型以及黑色素瘤的ras热点亚型的生存率更高。我们详细的反卷积和突变相关性分析揭示了35个治疗靶点和候选反应生物标志物假设（包括CASP8和RAS途径基因）。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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