|
KMID : 0939920220540030894
|
|
대한암학회지
2022 Volume.54 No. 3 p.894 ~ p.906
|
|
|
Genomic Sequencing for Bladder Urothelial Carcinoma and Its Clinical Implications for Immunotherapy
|
|
Kim Ryul
Hong Jung-Yong
Lee Jee-Yun
Kwon Ghee-Young
Jeong Byong-Chang
Park Se-Hoon
|
|
|
Abstract
|
|
|
Purpose: This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).
Materials and Methods: We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).
Results: We identified frequent molecular dysregulations in chromatin regulatory genes (KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1?positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1?negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1?positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1?positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.
Conclusion: Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.
|
|
|
KEYWORD
|
|
|
Urinary bladder neoplasms, Whole-exome sequencing, Whole-transcriptome sequencing, Immunotherapy, Dual blockade
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|