Research Paper Volume 12, Issue 12 pp 12051—12073

Identification of an immune-related long non-coding RNA signature and nomogram as prognostic target for muscle-invasive bladder cancer

Yuxuan Song1, *, , Donghui Jin2, *, , Jingyi Chen3, *, , Zhiwen Luo4, , Guangyuan Chen5, , Yongjiao Yang6, , Xiaoqiang Liu1, ,

  • 1 Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China
  • 2 Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
  • 3 Department of Gastroenterology and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
  • 4 Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • 5 The Second Clinical Medical School, Nanchang University, Nanchang 330006, Jiangxi, China
  • 6 Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
* Equal contribution

Received: February 20, 2020       Accepted: May 1, 2020       Published: June 24, 2020
How to Cite

Copyright © 2020 Song 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.


To identify an immune-related prognostic signature based on long non-coding RNAs (lncRNAs) and find immunotherapeutic targets for bladder urothelial carcinoma, we downloaded RNA-sequencing data from The Cancer Genome Atlas (TCGA) dataset. Functional enrichment analysis demonstrated bladder urothelial carcinoma was related to immune-related functions. We obtained 332 immune-related genes and 262 lncRNAs targeting immune-related genes. We constructed a signature based on eight lncRNAs in training cohort. Patients were classified as high-risk and low-risk according to signature risk score. High-risk patients had poor overall survival compared with low-risk patients (P < 0.001). Multivariate Cox regression suggested the signature was an independent prognostic indicator. The findings were further validated in testing, entire TCGA and external validation cohorts. Gene set enrichment analysis indicated significant enrichment of immune-related phenotype in high-risk group. Immunohistochemistry and online analyses validated the functions of 4 key immune-related genes (LIG1, TBX1, CTSG and CXCL12) in bladder urothelial carcinoma. Nomogram proved to be a good classifier for muscle-invasive bladder cancer through combining the signature. In conclusion, our immune-related prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for muscle-invasive bladder cancer.


BCa: bladder urothelial carcinoma; lncRNA: Long non-coding RNA; OS: Overall survival; TCGA: The Cancer Genome Atlas; BLCA: Bladder Urothelial Carcinoma; DEGs: Differentially expressed genes; CI: Confidence interval; HR: Hazard ratio; ROC: Receiver operating characteristic; AUC: Area under curve; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: Biological process; CC: Cell component; MF: Molecular function; UICC: Union for International Cancer Control; AIC: Akaike information criteria; KM: Kaplan-Meier; PCA: Principal component analysis; GSEA: Gene set enrichment analysis; FDR: False discovery rate; THPA: The Human Protein Atlas; CTSG: Cathepsin G; CXCL12: chemokine (C-X-C motif) ligand 12; LIG1: DNA Ligase 1; TBX1: T-Box Transcription Factor 1; GEPIA: Gene Expression Profiling Interactive Analysis; NES: Normalized enrichment score.