Transforming growth factor-β(TGF-β)signaling pathway-related genes in predicting the prognosis of colon cancer and guiding immunotherapy  

作　　者：Jie Chen Chao Ji Silin Liu Jin Wang Che Wang Jue Pan Jinyu Qiao Yu Liang Mengjiao Cai Jinlu Ma 

机构地区：[1]Department of Radiation Oncology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,Shaanxi 710061,China

出　　处：《Cancer Pathogenesis and Therapy》2024年第4期299-313,共15页癌症发生与治疗（英文）

基　　金：supported by grants from the Scientific Development Funding of the First Affiliated Hospital of Xi'an Jiaotong University(No.YXJLRH2022039 and No.2020QN-07);the Fundamental Research Funds for the Central Universities(No.xzy012020044);the Open Research Fund of Hubei Key Laboratory of Precision Radiation Oncolog(No.jzfs021).

摘　　要：Background:Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy.Transforming growth factor-β(TGF-β)signaling pathway-related genes are associated with multiple tumors,but their role in prognosis prediction and tumor microenvironment(TME)regulation in colon cancer is poorly understood.Using bioinformatics,this study aimed to construct a risk prediction signature for colon cancer,which may provide a means for developing new effective treatment strategies.Methods:Using consensus clustering,patients in The Cancer Genome Atlas(TCGA)with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-βsignaling pathway-related genes,and differences in survival,molecular,and immunological TME characteristics and drug sensitivity were examined in each subtype.Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation(LASSO)regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus(GEO)dataset.A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy.Results:Two TGF-βsubtypes were identified,with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy.Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype.After completing signature construction,patients with colon cancer were categorized into high-and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature.The risk score exhibited superior predictive performance relative to age,gender,and stage,as evidenced by its AUC of 0.686.Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME,suggesting that these patients had better responses to immunotherapy.Conc

关 键 词：Colon cancer PROGNOSIS Risk signature Immune microenvironment IMMUNOTHERAPY 

分 类 号：R735.3[医药卫生—肿瘤]