Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC  

作　　者：Lixuan Wang Rongchun Yang Yue Kong Jing Zhou Yingyao Chen Rui Li Chuwen Chen Xinran Tang Xiaobing Chen Juan Xia Xijuan Chen Bin Cheng Xianyue Ren 

机构地区：[1]Hospital of Stomatology,Sun Yat-Sen University,Guangzhou,China [2]Guangdong Provincial Key Laboratory of Stomatology,Guangzhou,China [3]Guanghua School of Stomatology,Sun Yat-Sen University,Guangzhou,China [4]Department of Radiation Oncology,Nanfang Hospital,Southern Medical University,Guangzhou,China

出　　处：《International Journal of Oral Science》2024年第4期711-727,共17页国际口腔科学杂志(英文版)

基　　金：supported by grants from the GuangDong Basic and Applied Basic Research Foundation(No.2023A1515030121,No.2021A1515111020,No.2023A1515010246);the National Natural Science Foundation of China(No.82273148,No.82103555,No.82301086);the Science and Technology Projects in Guangzhou(No.202206080009)。

摘　　要：Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine–glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

关 键 词：metabolism therapeutic precise 

分 类 号：R739.91[医药卫生—肿瘤]