Abstract

To explore novel therapeutic targets, develop a gene signature and construct a prognostic nomogram of bladder cancer (BCa). Transcriptome data and clinical traits of BCa were downloaded from UCSC Xena database and Gene Expression Omnibus (GEO) database. We then used the method of Single sample Gene Set Enrichment analysis (ssGSEA) to calculate the infiltration abundances of 24 immune cells in eligible BCa samples. By weighted correlation network analysis (WGCNA), we identified turquoise module with strong and significant association with the infiltration abundance of immune cells which were associated with overall survival of BCa patients. Subsequently, we developed an immune cell infiltration-related gene signature based on the module genes (MGs) and immune-related genes (IRGs) from the Immunology Database and Analysis Portal (ImmPort). Then, we tested the prognostic power and performance of the signature in both discovery and external validation datasets. A nomogram integrated with signature and clinical features were ultimately constructed and tested. Five prognostic immune cell infiltration-related module genes (PIRMGs), namely FPR1, CIITA, KLRC1, TNFRSF6B, and WFIKKN1, were identified and used for gene signature development. And the signature showed independent and stable prognosis predictive power. Ultimately, a nomogram consisting of signature, age and tumor stage was constructed, and it showed good and stable predictive ability on prognosis. Our prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for BCa. Further researches are needed to verify the clinical effectiveness of this nomogram and these biomarkers.

Highlights

  • To explore novel therapeutic targets, develop a gene signature and construct a prognostic nomogram of bladder cancer (BCa)

  • The infiltration abundance of CD8 T cells, was significantly higher in muscle-invasive bladder cancer (MIBC), which may be influenced by the basis of small sample size of non- muscle-invasive bladder cancer (NMIBC)

  • We identified five prognostic immune cell infiltration-related module genes (PIRMGs) (FPR1, CIITA, KLRC1, TNFRSF6B, and WFIKKN1) from the turquoise module which showed positive and significant correlations with several immune cells including CD8+ T cells

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Summary

Introduction

To explore novel therapeutic targets, develop a gene signature and construct a prognostic nomogram of bladder cancer (BCa). By weighted correlation network analysis (WGCNA), we identified turquoise module with strong and significant association with the infiltration abundance of immune cells which were associated with overall survival of BCa patients. We developed an immune cell infiltration-related gene signature based on the module genes (MGs) and immunerelated genes (IRGs) from the Immunology Database and Analysis Portal (ImmPort). Five prognostic immune cell infiltration-related module genes (PIRMGs), namely FPR1, CIITA, KLRC1, TNFRSF6B, and WFIKKN1, were identified and used for gene signature development. A nomogram consisting of signature, age and tumor stage was constructed, and it showed good and stable predictive ability on prognosis.

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