Identification and validation of RB1 as an immune-related prognostic signature based on tumor mutation burdens in bladder cancer

• Published in: Anti-cancer drugs
• Main Authors: Liu, Ning, Wu, Tiange, Ma, Yuexian, Cheng, Hong, Li, Wenchao, Chen, Ming
• Format: Journal Article
• Language: English
• Published: The Author(s). Published by Wolters Kluwer Health, Inc 06-10-2022
• ISSN: 0959-4973
• DOI: 10.1097/CAD.0000000000001399

Bladder cancer (BCa) is one of the most common malignant tumors in the urinary system. Developing effective prognostic gene and exploring the immune cells that affect the prognosis of tumor are required. Full transcriptome data (n = 433), clinical information (n = 581) and mutation sequencing (n = 412) were obtained from The Cancer Genome Atlas and independent mutation sequencing data of 101 samples were acquired from International Cancer Genome Consortium. Statistical processing was conducted using R packages. Gene biologically functional research was performed with gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes database. Twenty-two types of immune cell infiltration were assessed and calculated in 398 samples of BCa. Furthermore, the expression of immune-related prognostic signature was verified. The relationship between prognostic gene and immune cells was explored preliminarily. Tumor mutation burdens of mutant-type groups were higher than wild-type groups of 19 genes, except for FGFR3 and CREBBP. Kaplan–Meier analysis showed that high frequency of retinoblastomal 1 (RB1) mutation led to poor prognosis of BCa patients and was an independent prognostic factor (P = 0.004; HR = 1.776). Proportions and correlation of 22 types of immune cells in 433 samples were determined. We found that RB1 expression decreased in BCa validated through quantitative PCR and immunohistochemistry. In addition, regulatory T cells (Tregs) were detected as a negatively correlated type of immune cell to mutation of RB1, whereas fluorescence costaining showed that Foxp3 expression of Tregs infiltration was negatively related to the expression of RB1. Mutation of RB1 can be identified as an independent prognostic predictor of BCa, and it may suppress the infiltration of Tregs in BCa tissues, increasing the incidence of tumor immune escape.