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학술저널
저자정보
김률 (삼성서울병원) 홍정용 (성균관대학교) 이지연 (성균관대학교) 권기영 (삼성서울병원) 정병창 (성균관대학교) 박세훈 (성균관대학교)
저널정보
대한암학회 Cancer Research and Treatment Cancer Research and Treatment 제54권 제3호
발행연도
2022.7
수록면
894 - 906 (13page)
DOI
10.4143/crt.2021.854

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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 (<i>KDM6A, ARID1A, MLL2,</i> and <i>STAG2</i>) 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.

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