Research Paper Advance Articles

Identification of immune-related LncRNA for predicting prognosis and immunotherapeutic response in bladder cancer

Yucai Wu1,2,3,4, *, , Lei Zhang1,2,3,4, *, , Shiming He1,2,3,4, , Bao Guan1,2,3,4, , Anbang He1,2,3,4, , Kunlin Yang1,2,3,4, , Yanqing Gong1,2,3,4, , Xuesong Li1,2,3,4, , Liqun Zhou1,2,3,4, ,

  • 1 Department of Urology, Peking University First Hospital, Beijing, China
  • 2 Institute of Urology, Peking University, Beijing, China
  • 3 National Urological Cancer Center, Beijing, China
  • 4 Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
* Equal contribution

Received: June 29, 2020       Accepted: September 9, 2020       Published: November 18, 2020      

https://doi.org/10.18632/aging.104115
How to Cite

Copyright: © 2020 Wu 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

Long noncoding RNAs (lncRNAs) have multiple functions in the cancer immunity response and the tumor microenvironment. To investigate the immune-related lncRNA (IRlncRNA) signature for predicting prognosis and immunotherapeutic response in bladder cancer (BLCA), we extracted BLCA data from The Cancer Genome Atlas (TCGA) database. Finally, a total of 405 cases were enrolled and 8 prognostic IRlncRNAs (MIR181A2HG, AC114730.3, LINC00892, PTPRD-AS1, LINC01013, MRPL23-AS1, LINC01395, AC002454.1) were identified in the training set. Risk scores were calculated to divide patients into high-risk and low-risk groups, and the high-risk patients tended to have a poor overall survival (OS). Multivariate Cox regression analysis confirmed that the IRlncRNA signature could be an independent prognostic factor. The results were subsequently confirmed in the validating set. Additionally, this 8-IRlncRNA classifier was related to recurrence free survival (RFS) of BLCA. Functional characterization revealed this signature mediated immune-related phenotype. This signature was also associated with immune cell infiltration (i.e., macrophages M0, M2, Tregs, CD8 T cells, and neutrophils) and immune checkpoint inhibitors (ICIs) immunotherapy-related biomarkers [mismatch repair (MMR) genes, tumor mutation burden (TMB) and immune checkpoint genes]. The present study highlighted the value of the 8-IRlncRNA signature as a predictor of prognosis and immunotherapeutic response in BLCA.

Abbreviations

BLCA: Bladder cancer; ccRCC: Clear cell renal cell carcinoma; OS: Overall survival; IRlncRNA: Immune-related lncRNA; RFS: Recurrence-free survival; TCGA: The Cancer Genome Atlas; LASSO: Least absolute shrinkage and selection operator; ICIs: Immune checkpoint inhibitors; SNV: Single nucleotide variation; FPKM: Fragments per Kilobase Million; DElncRNAs: Differentially expressed lncRNAs; CIBERSOFT: Cell-type Identification by Estimating Relative Subsets of RNA Transcripts; GSEA: Gene set enrichment analysis; MMR: Mismatch repair; TMB: Tumor mutation burden; ROC: Receiver operating character; AUCs: Area under curve; NMIBC: Non–muscle-invasive bladder cancer; MIBC: Muscle-invasive bladder cancer; miRNAs: MicroRNAs; LncRNAs: Long non-coding RNAs; circRNAs: Circular RNAs; FD: Fold change; FDR: False discovery rate.