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

作     者：Peidong Zhang Peiwei Li Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou 

作者机构：Department of Obstetrics and GynecologyKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOEState Key Laboratory of BiotherapyWest China Second HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Physician Scientist Training ProgramDepartment of MedicineWashington University School of MedicineSt.Louis 63110USA Department of NeurosurgeryState Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Department of Radiation OncologyTaussig Cancer CenterCleveland ClinicCleveland 44106USA 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2024年第67卷第8期

页      面：1549-1562页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(82325039,82273255,81822034,81821002) the National Key Research and Development Program of China(2022YFA1106600) Sichuan Science-Technology Project(2022ZYD0054,2019YFH0144) Direct Scientific Research Grants from West China Second Hospital,Sichuan University(KS021,K1907) Young Investigator Award in Glioblastoma from ASCO Conquer Cancer Foundation(ASCO2018JS) RSNA Research Resident Grant(RR2166) 

主　　题：pan-cancer cancer mechanics multi-omics immunology 

摘      要：Mechanics shape cell and tissue plasticity and maintain their *** cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic ***,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains ***,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)*** the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway *** subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical *** 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 ***,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.