Analysis of prognostic oncogene filaggrin () wild-type subtype and its implications for immune checkpoint blockade therapy in bladder urothelial carcinoma.

BACKGROUND

Bladder urothelial carcinoma (BLCA) is one of the most common urinary tract malignant tumors. Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of BLCA. This study aimed to investigate the role of specific genetic mutations that may serve as immune biomarkers for ICB therapy in BLCA.

METHODS

Mutation information and expression profiles were acquired from The Cancer Genome Atlas (TCGA) database. Integrated bioinformatics analysis was carried out to explore the subtypes with poor prognosis of BLCA. Functional enrichment analysis was also conducted. The infiltrating immune cells and the prediction of ICB response between different subtypes were explored using the immuCellAI algorithm. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted to explore the effect of filaggrin () knockdown in BLCA 5637 and T24 cell lines.

RESULTS

An overview of mutation information in BLCA patients was shown. was identified to be strongly associated with the prognosis of BLCA patients and wild-type was associated with poorer outcome. Prognostic wild-type was divided into 2 subtypes (Sub1 and Sub2). Following an investigation of the subtypes, Sub2 of wild-type was found to be associated with poorer outcome in BLCA. The differentially expressed genes (DEGs) between Sub1 and Sub2 were screened out and the DEGs were enriched in malignant tumor proliferation, DNA damage repair, and immune-related pathways. Furthermore, Sub2 of wild-type was associated with infiltrated immune cells, and responded worse to ICB. Sub2 of wild-type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. The cellular experiments revealed that knockdown of could suppress BLCA cell proliferation and promote apoptosis.

CONCLUSIONS

is an oncogene that may affect the prognosis of BLCA patients through mutation. Sub2 of wild-type is associated with poor prognosis and can be used to predict ICB response for BLCA treatment. This research provides a new basis and ideas for guiding the clinical application of BLCA immunotherapy.