Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma
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Melanoma-associated antigen-A (MAGE-A) and programmed-death ligand 1 (PD-L1) are present in urothelial carcinoma (UC). We assessed survival outcomes in patients with MAGE-A and PD-L1 expression.
MAGE-A and PD-L1 expression on neoplastic cells was analyzed using tissue microarrays from patients with UC. We compared differential expression between disease stage and grade. MAGE-A and PD-L1 co-expression was subcategorized. Fisher’s exact test was done for categorical variables followed by univariable and multivariable analysis of recurrence-free survival (RFS) and progression-free survival (PFS).
Co-expression of MAGE+/PD-L1+ was higher in advanced disease; however, only MAGE+/PD-L1− was associated with shorter RFS [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.19–2.99; p = .006]. MAGE+/PD-L1+ was associated with the worst PFS (HR 17.1; 95% CI 5.96–49.4; p ≤ .001). MAGE-A expression was more prevalent with high-grade (p = .015), and higher-stage ≥ pT2 (p = .001) disease. The 5-year RFS was 44% for MAGE+ versus 58% for MAGE− patients. On multivariable analysis, MAGE+ was also associated with shorter RFS (HR 1.55; 95% CI 1.05–2.30; p = .03). Similarly, MAGE+ was associated with shorter PFS (HR 3.12; 95% CI 1.12–8.68; p = .03).
MAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+ provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings.
KeywordsUrothelial carcinoma Melanoma-associated antigen Programmed death-ligand 1 Tissue microarray Survival
Programmed death-ligand 1
Adoptive T-cell receptor-engineered T-cell therapy
IF: Conception, data collection, data analysis, drafting manuscript, critical revisions. SHA: Conception, drafting manuscript, critical revisions. DAE: Data analysis, drafting manuscript, critical revisions. RJ: Drafting manuscript, critical revisions. AB: Conception, drafting manuscript, critical revisions. KC: Conception, drafting manuscript, critical revisions. ASB MD: Conception, critical revisions. AJP: Conception, drafting manuscript, critical revisions. AD: Conception, drafting manuscript, critical revisions.
Research funding was provided by Kite, a Gilead Company. Biomedical editing was sponsored by Kite, a Gilead Company.
Compliance with ethical standards
Conflict of interest
Izak Faiena and Alexandra Drakaki received research funding from Kite, a Gilead Company. Stephanie H. Astrow, Rajul Jain, and Adrian Bot are employees of Kite, a Gilead Company, and have equity ownership in Gilead Sciences, Inc. Arie S. Belldegrun is the founder and was formerly Chief Executive Officer of Kite, a Gilead Company, and has equity ownership in Gilead Sciences, Inc. Allan J. Pantuck has equity ownership in Gilead Sciences, Inc. The authors declare they have no other conflicts of interest.
Ethical approval and ethical standards
This study included de-identified data in a tissue microarray and was deemed to be an exempt study by the institutional review board (IRB #99–233) of the University of California, Los Angeles for TMA construction and data analysis; therefore, special ethical permission was not required. Requirement for consent was waived given the retrospective, de-identified nature of the samples, and the impracticality of consenting for samples stored prior to 1998.
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