Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer

Frontiers in Cell and Developmental Biology

卷:9

Jiefei Xiao¹  Yongkang Ye²  Yong Huang³  Zhuangyao Liao³  Jiaying Li³  Mingxiao Zhang³  Chengpeng Gui³  Jinhuan Wei³  Wei Chen³  Lei Tan³  Yiming Tang³  Xu Chen³  Jiazheng Cao⁴  Junhang Luo⁵  Pengju Li⁵  Shihui Hao⁶ 

[1] Department of Extracorporeal Circulation, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;

[2] Department of Urology, Dongguan People’s Hospital, Affiliated to Southern Medical University, Dongguan, China;

[3] Department of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;

[4] Department of Urology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yet-sen University, Jiangmen, China;

[5] Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;

[6] State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;

关键词: immune-related risk signature;    immunity gene;    immune checkpoint inhibitor;    urothelial cancer;    tumor microenvironment;   

DOI  :  10.3389/fcell.2021.646982

来源: DOAJ

【 摘 要 】

Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p < 0.0001), 2.56 (p < 0.0001), 3.36 (p < 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.

【 授权许可】

Unknown