Identification of an Immune Gene-associated Prognostic Signature in Patients with Bladder Cancer

Overview

Journal Cancer Gene Ther

Specialties Genetics
Oncology
Pharmacology

Date 2022 Feb 16

PMID 35169299

Authors

Zhiqiang Wang

Liping Zhu

Li Li

Justin Stebbing

Zibing Wang

Ling Peng

Affiliations

Soon will be listed here.

Abstract

A deeper understanding of the interaction between tumor cell and the immune microenvironment in bladder cancer may help select predictive and prognostic biomarkers. The current study aims to construct a prognostic signature for bladder cancer by analysis of molecular characteristics, as well as tumor-immune interactions. RNA-sequencing and clinical information from bladder cancer patients were downloaded from the TCGA database. The single sample Gene Sets Enrichment Analysis (ssGSEA) and Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) were employed to separate the samples into two clusters. Lasso Cox regression was performed to construct an immune gene signature for bladder cancer. The correlation between key target genes of immune checkpoint blockade and the prognostic signature was also analyzed. Dataset from Gene Expression Omnibus (GEO) was retrieved for validation. Two immunophenotypes and immunological characteristics were identified, and a 17-immune gene signature was constructed to provide an independent prognostic signature for bladder cancer. The signature was verified through external validation and correlated with genomic characteristics and clinicopathologic features. Finally, a nomogram was generated from the clinical characteristics and immune signature. Our study reveals a tumor-immune microenvironment signature useful for prognosis in bladder cancer. The results provide information on the potential development of treatment strategies for bladder cancer patients. Prospective studies are warranted to validate the prognostic capability of this model, but these data highlight the role of the microenvironment in the clinical outcome of patients.

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References

Pang K, Esperto F, Noon A . Opportunities of next-generation sequencing in non-muscle invasive bladder cancer outcome prediction. Transl Androl Urol. 2018; 6(6):1043-1048. PMC: 5760392. DOI: 10.21037/tau.2017.10.04. View

Bellmunt J, Powles T, Vogelzang N . A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now. Cancer Treat Rev. 2017; 54:58-67. DOI: 10.1016/j.ctrv.2017.01.007. View

Jiang W, Zhu D, Wang C, Zhu Y . An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle-invasive bladder cancer (MIBC). Cancer Med. 2020; 9(8):2774-2790. PMC: 7163112. DOI: 10.1002/cam4.2942. View

Balar A, Galsky M, Rosenberg J, Powles T, Petrylak D, Bellmunt J . Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 389(10064):67-76. PMC: 5568632. DOI: 10.1016/S0140-6736(16)32455-2. View

Song B, Kim S, Mun J, Choi Y, Leem S, Chu I . Identification of an immunotherapy-responsive molecular subtype of bladder cancer. EBioMedicine. 2019; 50:238-245. PMC: 6921227. DOI: 10.1016/j.ebiom.2019.10.058. View

Zhou T, Sankin A, Porcelli S, Perlin D, Schoenberg M, Zang X . A review of the PD-1/PD-L1 checkpoint in bladder cancer: From mediator of immune escape to target for treatment. Urol Oncol. 2016; 35(1):14-20. DOI: 10.1016/j.urolonc.2016.10.004. View

McConkey D, Choi W, Shen Y, Lee I, Porten S, Matin S . A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin,.... Eur Urol. 2015; 69(5):855-62. PMC: 4775435. DOI: 10.1016/j.eururo.2015.08.034. View

Tan T, Rouanne M, Tan K, Huang R, Thiery J . Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort Analysis of 2411 Tumors. Eur Urol. 2018; 75(3):423-432. DOI: 10.1016/j.eururo.2018.08.027. View

Hedegaard J, Lamy P, Nordentoft I, Algaba F, Hoyer S, Ulhoi B . Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer Cell. 2016; 30(1):27-42. DOI: 10.1016/j.ccell.2016.05.004. View

10.

Kamoun A, De Reynies A, Allory Y, Sjodahl G, Robertson A, Seiler R . A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol. 2019; 77(4):420-433. PMC: 7690647. DOI: 10.1016/j.eururo.2019.09.006. View

11.

Liu J, Ma H, Meng L, Liu X, Lv Z, Zhang Y . Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer. Front Mol Biosci. 2021; 8:675651. PMC: 8175978. DOI: 10.3389/fmolb.2021.675651. View

12.

Wang X, Pan L, Lu Q, Huang H, Feng C, Tao Y . A combination of ssGSEA and mass cytometry identifies immune microenvironment in muscle-invasive bladder cancer. J Clin Lab Anal. 2021; 35(5):e23754. PMC: 8128294. DOI: 10.1002/jcla.23754. View

13.

Zhao K, Zhang Q, Zeng T, Zhang J, Song N, Wang Z . Identification and validation of a prognostic immune-related lncRNA signature in bladder cancer. Transl Androl Urol. 2021; 10(3):1229-1240. PMC: 8039609. DOI: 10.21037/tau-20-1353. View

14.

Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W . Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013; 4:2612. PMC: 3826632. DOI: 10.1038/ncomms3612. View

15.

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

16.

Kobak D, Berens P . The art of using t-SNE for single-cell transcriptomics. Nat Commun. 2019; 10(1):5416. PMC: 6882829. DOI: 10.1038/s41467-019-13056-x. View

17.

Bhattacharya S, Dunn P, Thomas C, Smith B, Schaefer H, Chen J . ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Sci Data. 2018; 5:180015. PMC: 5827693. DOI: 10.1038/sdata.2018.15. View

18.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

19.

Mootha V, Lindgren C, Eriksson K, Subramanian A, Sihag S, Lehar J . PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003; 34(3):267-73. DOI: 10.1038/ng1180. View

20.

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View