Identification of NTRK3 as a potential prognostic biomarker associated with tumor mutation burden and immune infiltration in bladder cancer

Zhao Zhang,Haitao Niu,Ye Liang,Yongbo Yu,Wei Jiao,Mingxin Zhang,Guofeng Ma,Pengfei Zhang

doi:10.1186/s12885-021-08229-1

Zhao Zhang, Haitao Niu + Show 6 more

Open Access

https://doi.org/10.1186/s12885-021-08229-1

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Abstract

BackgroundBladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy has played a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker for predicting tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to identify the key genes in BLCA.MethodsClinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups according to their calculated TMB scores. Gene Set Enrichment Analysis (GSEA) was performed to screen for significantly enriched pathways. Differentially expressed genes (DEGs) between the two groups were identified. Univariate Cox analysis and Kaplan-Meier survival analysis were applied for screening key genes. Immune infiltration was performed for TMB groups and NTRK3.ResultsHigher TMB scores were related with poor survival in BLCA. After filtering, 36 DEGs were identified. NTRK3 had the highest hazard ratio and significant prognostic value. Co-expressed genes of NTRK3 were mainly involved in several pathways, including DNA replication, basal transcription factors, complement and coagulation cascades, and ribosome biogenesis in eukaryotes. There was a significant correlation among TMB scores, NTRK3 expression and immune infiltration.ConclusionsOur results suggest that NTRK3 is a TMB-related prognostic biomarker, which lays the foundation for further research on the immunomodulatory effect of NTRK3 in BLCA.

Highlights

Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality
Many studies have shown that the tumor mutation burden (TMB) is a powerful biomarker for predicting the efficacy of Immune checkpoint inhibitor (ICI) and can be used to identify patients who will benefit from immunotherapy [13]
Screening of key genes associated with Tumor mutation burden (TMB) and survival We identified the differentially expressed genes (DEGs) between high and low TMB groups

Summary

Introduction

Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. Treatment with ICIs such as antiprogrammed cell death protein 1(PD-1), antiprogrammed death-ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can significantly increase OS and result in durable remission for many advanced cancers, including melanoma, non-small cell lung cancer, renal cancer and urothelial cancer [9,10,11,12] These effects only exist in a small subset of patients who can respond to ICIs. Many studies have shown that the tumor mutation burden (TMB) is a powerful biomarker for predicting the efficacy of ICIs and can be used to identify patients who will benefit from immunotherapy [13]. Exploring the relationship between TMB and immunoregulation and discovering the related genes or biological mechanisms will help to better understand the role of immunotherapy in cancer treatment

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