Abstract
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. 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 (FLG) knockdown in BLCA 5637 and T24 cell lines. An overview of mutation information in BLCA patients was shown. FLG was identified to be strongly associated with the prognosis of BLCA patients and FLG wild-type was associated with poorer outcome. Prognostic FLG wild-type was divided into 2 subtypes (Sub1 and Sub2). Following an investigation of the subtypes, Sub2 of FLG 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 FLG wild-type was associated with infiltrated immune cells, and responded worse to ICB. Sub2 of FLG wild-type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. The cellular experiments revealed that knockdown of FLG could suppress BLCA cell proliferation and promote apoptosis. FLG is an oncogene that may affect the prognosis of BLCA patients through mutation. Sub2 of FLG 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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
