Immune-related gene signature associates with immune landscape and predicts prognosis accurately in patients with Wilms tumour

作者全名："Tian, Xiao-Mao; Xiang, Bin; Jin, Li-Ming; Mi, Tao; Wang, Jin-Kui; Zhanghuang, Chenghao; Zhang, Zhao-Xia; Chen, Mei-Ling; Shi, Qin-Lin; Liu, Feng; Lin, Tao; Wei, Guang-Hui"

作者地址："[Tian, Xiao-Mao; Xiang, Bin; Jin, Li-Ming; Mi, Tao; Wang, Jin-Kui; Zhang, Zhao-Xia; Chen, Mei-Ling; Shi, Qin-Lin; Liu, Feng; Lin, Tao; Wei, Guang-Hui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing, Peoples R China; [Tian, Xiao-Mao; Xiang, Bin; Jin, Li-Ming; Mi, Tao; Wang, Jin-Kui; Zhanghuang, Chenghao; Zhang, Zhao-Xia; Chen, Mei-Ling; Shi, Qin-Lin; Liu, Feng; Lin, Tao; Wei, Guang-Hui] Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Natl Clin Res Ctr Child H, Chongqing, Peoples R China; [Tian, Xiao-Mao; Xiang, Bin; Jin, Li-Ming; Mi, Tao; Wang, Jin-Kui; Zhanghuang, Chenghao; Zhang, Zhao-Xia; Chen, Mei-Ling; Shi, Qin-Lin; Liu, Feng; Wei, Guang-Hui] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China"

通信作者："Liu, F (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing, Peoples R China.; Liu, F (通讯作者)，Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Natl Clin Res Ctr Child H, Chongqing, Peoples R China.; Liu, F (通讯作者)，Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000860988900001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Wilms tumour; immune signature; tumour immune microenvironment; prognosis; immunotherapy

摘要："Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint."

基金机构："Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0345, cstc2021jcyj-msxm-X0549]; Medical Scientific Research Project of Chongqing [2022GDRC009]; general project of clinical medicine research of Children's Hospital of Chongqing Medical University [NCRC-2019-GP-08]"

基金资助正文："This work was supported by the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0345 and cstc2021jcyj-msxm-X0549), the Medical Scientific Research Project of Chongqing (NO.2022GDRC009), the general project of clinical medicine research of Children's Hospital of Chongqing Medical University (NCRC-2019-GP-08)."