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

Abstract

Background Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy plays a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker to predict tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to excavate the key genes in BLCA. Methods Clinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. According to the calculated TMB scores, patients were divided into high and low TMB groups. Gene Set Enrichment Analysis (GSEA) was performed to screen 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. Results Higher 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. Conclusions Our 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.

Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors

“…Exploring gene mutations related to better OS, NTRK3 protein expression was previously positively associated with higher tumor immune and stromal scores, a great variety of immune lymphocytes, improved immune response, and, ultimately, with better survival. Accordingly, NTRK3 might be a novel biomarker for ICI outcomes in selected tumor types [ 20 ] (p. 3). The PTPRD gene encodes protein tyrosine phosphatase receptor type D (PTPRD), which is related to an increased mRNA expression of JAK1 and STAT1 subsequently attracting T cells through chemokines overexpression.…”

Interplay between Tumor Mutational Burden and Mutational Profile and its effect on overall survival: A Post Hoc Analysis of Metastatic Patients Treated with Immune Checkpoint Inhibitors

“…Exploring gene mutations related to better OS, NTRK3 protein expression was previously positively associated with higher tumor immune and stromal scores, a great variety of immune lymphocytes, improved immune response, and ultimately with better survival. Accordingly, NTRK3 may be a novel biomarker for ICI outcomes in selected tumor types 20(p3) . The PTPRD gene encodes protein tyrosine phosphatase receptor type D (PTPRD) which is related to an increased mRNA expression of JAK1 and STAT1, subsequently attracting T cells through chemokines overexpression.…”