The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

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外文摘要：Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogramming.However,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched.Herein,we sys-tematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)databases.All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes.Each subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical outcome.We further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents.Collectively,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

外文关键词：

pan-cancercancer mechanicsmulti-omicsimmunology

作者：

Peidong Zhang、Peiwei Li、Muya Tang、Ryan C.Gimple、Liang Huang、Jing Yue、Qiuhong Shen、Yiwei Du、Qian Zhang、Zhengnan Yang、Haihuai He、Kailin Yang、Linjie Zhao、Shengtao Zhou

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作者单位：

Department of Obstetrics and Gynecology,Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE,State Key Laboratory of Biotherapy,West China Second Hospital,Sichuan University and Collaborative Innovation Center,Chengdu 610041,China

Physician Scientist Training Program,Department of Medicine,Washington University School of Medicine,St.Louis 63110,USA

Department of Neurosurgery,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University and Collaborative Innovation Center,Chengdu 610041,China

Department of Radiation Oncology,Taussig Cancer Center,Cleveland Clinic,Cleveland 44106,USA

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaSichuan Science-Technology ProjectSichuan Science-Technology ProjectDirect Scientific Research Grants from West China Second Hospital.Sichuan UniversityDirect Scientific Research Grants from West China Second Hospital.Sichuan UniversityYoung Investigator Award in Glioblastoma from ASCO Conquer Cancer FoundationRSNA Research Resident Grant

项目编号：

823250398227325581822034818210022022YFA11066002022ZYD00542019YFH0144KS021K1907ASC02018JSRR2166

出版年：

2024

DOI：

10.1007/s11427-024-2622-1

中国科学:生命科学(英文版)

中国科学院

中国科学:生命科学(英文版)

CSTPCD

影响因子：0.806

ISSN：1674-7305

年,卷(期)：2024.67(8)

参考文献量2