Comprehensive Gene Expression Analyses of Immunohistochemically Defined Subgroups of Muscle-Invasive Urinary Bladder Urothelial Carcinoma

International Journal of Molecular Sciences

Insoon Jang¹  YoungA. Kim²  JeongHwan Park²  Minsun Jung³  Bohyun Kim³  Cheol Lee³  KyungChul Moon³  Kwangsoo Kim⁴ 

[1] Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea;Department of Pathology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 03080, Korea;Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea;Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul 03080, Korea;

关键词: muscle invasive bladder cancer;    molecular classification;    cytokeratin 5/6;    cytokeratin 20;   

DOI  :  10.3390/ijms22020628

来源: DOAJ

【 摘 要 】

A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. The results of gene ontology (GO) terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, interleukin 6-Janus kinase-signal transducer and activator of transcription 3 (IL6-JAK-STAT3) signaling pathway and tumor necrosis factor-α signaling via the nuclear factor-κB (NF-κB) signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival (p = 0.008). The results of our study indicate that the CK5/6 positive subgroup exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.

【 授权许可】

Unknown