Research Paper Volume 14, Issue 3 pp 1492—1507

Identification and validation of a twelve immune infiltration-related lncRNA prognostic signature for bladder cancer

Chen-Qian Liu1, *, , Qi-Dong Xia1, *, , Jian-Xuan Sun1, , Jin-Zhou Xu1, , Jun-Lin Lu1, , Zheng Liu1, , Jia Hu1, , Shao-Gang Wang1, ,

  • 1 Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
* Co-first authors

Received: January 1, 2021       Accepted: February 2, 2022       Published: February 14, 2022
How to Cite

Copyright: © 2022 Liu 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.


The prognosis of bladder cancer patients is strongly related to both the immune-infiltrating cells and the expression of lncRNAs. In this study, we analyzed the infiltration of immune cells in 403 bladder cancer samples obtained from TCGA by applying the ssGSEA to these samples, then dividing them into high/low immune cell infiltration groups. Based on these groupings, we found 404 differentially expressed immune infiltration-related lncRNAs, which were successively analyzed by univariate Cox regression, then Least Absolute Shrinkage and Selection Operator (LASSO), and finally stepwise multiple Cox regression. Then 12 differentially expressed immune infiltration-related lncRNAs were identified and used to construct a prognostic signature for bladder cancer. Subsequently, Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, and multivariate time-dependent ROC analyses (for 1, 3, 5 years) all revealed that this signature performed well in predicting overall survival and served as an independent prognostic factor for patients with bladder cancer. Finally, both TIMER and CIBESORT showed that this 12-lncRNA prognostic signature for bladder cancer was associated with the infiltration of immune cell subtypes. Besides, nomogram considered risk score and clinical characteristics was assembled and showed great performance. More importantly, we found our signature could well distinguish the drug response of patients with bladder cancer. High risk patients showed a better response to cisplatin, doxorubicin, and anti- CTLA4 immunotherapy, low risk patients showed a better response to methotrexate and anti-PD1 immunotherapy compared with each other.


LASSO: Least Absolute Shrinkage and Selection Operator; BC: Bladder cancer; TME: tumor microenvironment; LncRNA: Long non-coding RNA; DC: Dendritic cells; APC: antigen-presenting cells; DFS: disease-free survival; RFS: relapse-free survival; DSS: disease-specific survival; TCGA: the Cancer Genome Atlas; ssGSEA: single-sample gene set enrichment analysis; FPKM: fragments per kilobase of per million format; GSVA: Gene Set Variation Analysis; DEG: differentially expressed genes.