Research Paper Volume 13, Issue 9 pp 13023—13038

A zinc finger protein gene signature enables bladder cancer treatment stratification

Jiandong Zhang1,2, *, , Chen Zhang3, *, , Peng Cao1, , Xiang Zheng1, , Baozhong Yu1, , Haoyuan Cao1, , Zihao Gao1, , Feilong Zhang1, , Jiyuan Wu1, , Huawei Cao1, , Changzhen Hao1, , Zejia Sun1, , Wei Wang1, ,

  • 1 Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing 100020, China
  • 2 Shanxi Bethune Hospital Affiliated Shanxi Academy of Medical Sciences, Taiyuan 030032, China
  • 3 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences and University of Chinese Academy of Sciences, Beijing 100101, China
* Equal contribution

Received: December 23, 2020       Accepted: March 31, 2021       Published: May 7, 2021
How to Cite

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.


BC: bladder cancer; ZNFs: zinc finger proteins; ZNF830: zinc finger protein 830; DEGs: differentially expressed genes; FDR: false discovery rate; OS: overall survival; TNM: tumor-node-metastasis; AUC: area under the curve; ROC: receiver operating characteristic; KEGG: Kyoto Encyclopedia of Genes and Genomes; GEO: Gene Expression Omnibus; GSEA: gene set enrichment analysis; ssGSEA: single-sample gene set enrichment analysis; GDSC: Genomics of Drug Sensitivity in Cancer; ZHX3: zinc fingers and homeoboxes 3; ZNF350: zinc finger protein 350; ZNRD1: zinc ribbon domain-containing 1; ZNF195: zinc finger protein 195; SUZ12: SUZ12 polycomb repressive complex 2 subunit; APEX2: apurinic/apyrimidinic endodeoxyribonuclease 2; EBF4: EBF family member 4; ZNRD1-AS1: zinc ribbon domain containing 1 antisense RNA 1.