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

¹Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China
²Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
³Department of Gastroenterology and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
⁴Department 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
⁵The Second Clinical Medical School, Nanchang University, Nanchang 330006, Jiangxi, China
⁶Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China

* Equal contribution

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

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.

Abstract

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.