Proteomic, single-cell and bulk transcriptomic analysis of plasma and tumor tissues unveil core proteins in response to anti-PD-L1 immunotherapy in triple negative breast cancer

被引：0
作者：
Li Y. [1 ,7 ]
Yue L. [2 ,3 ,4 ]
Zhang S. [5 ]
Wang X. [6 ]
Zhu Y.-N. [1 ]
Liu J. [1 ]
Ren H. [1 ]
Jiang W. [2 ,3 ,4 ]
Wang J. [6 ]
Zhang Z. [7 ,8 ]
Liu T. [1 ,7 ]
机构：
[1] Department of Oncological Surgery, Harbin Medical University Cancer Hospital, Heilongjiang Province, Harbin
[2] Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Zhejiang Province, Hangzhou
[3] Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Zhejiang Province, Hangzhou
[4] Research Center for Industries of the Future, Westlake University, 600 Dunyu Road, Zhejiang, Hangzhou
[5] Department of Neurobiology, Harbin Medical University, Heilongjiang Province, Harbin
[6] Department of Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang Province, Harbin
[7] NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin
[8] Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Heilongjiang Key Laboratory for Metabolic Disorder and Cancer Related Cardiovascular Diseases, Harbin
来源：
Computers in Biology and Medicine | 2024年 / 176卷
基金：
中国国家自然科学基金;
关键词：
COMP; Complement system; FAP; PD-1/PD-L1; TNBC;
D O I：
10.1016/j.compbiomed.2024.108537
中图分类号：
学科分类号：
摘要：
Background: Anti-PD-1/PD-L1 treatment has achieved durable responses in TNBC patients, whereas a fraction of them showed non-sensitivity to the treatment and the mechanism is still unclear. Methods: Pre- and post-treatment plasma samples from triple negative breast cancer (TNBC) patients treated with immunotherapy were measured by tandem mass tag (TMT) mass spectrometry. Public proteome data of lung cancer and melanoma treated with immunotherapy were employed to validate the findings. Blood and tissue single-cell RNA sequencing (scRNA-seq) data of TNBC patients treated with or without immunotherapy were analyzed to identify the derivations of plasma proteins. RNA-seq data from IMvigor210 and other cancer types were used to validate plasma proteins in predicting response to immunotherapy. Results: A random forest model constructed by FAP, LRG1, LBP and COMP could well predict the response to immunotherapy. The activation of complement cascade was observed in responders, whereas FAP and COMP showed a higher abundance in non-responders and negative correlated with the activation of complements. scRNA-seq and bulk RNA-seq analysis suggested that FAP, COMP and complements were derived from fibroblasts of tumor tissues. Conclusions: We constructe an effective plasma proteomic model in predicting response to immunotherapy, and find that FAP+ and COMP+ fibroblasts are potential targets for reversing immunotherapy resistance. © 2024 The Authors
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