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Association of Melanoma-Associated Antigen-A and Program-death ligand 1 Expression and Clinical Outcomes in Urothelial Carcinoma


Background: The melanoma-associated antigen-A (MAGE-A) and program-death ligand 1 (PD-L1) are present in urothelial carcinoma (UC). We aim to assess survival outcomes in patients with MAGE-A and PD-L1 expression.

Methods: Analysis of MAGE-A and PD-L1 expression on neoplastic cells was conducted using tissue microarrays from patients with UC. We compared differential expression between stage and grade. Co-expression of MAGE-A and PD-L1 were sub-categorized. Fisher’s exact test was done for categorical variables followed by analysis of univariable and multivariable assessment of recurrence and progression free survival (RFS, PFS).

Results: Co-expression of MAGE+/PD-L1+ had a higher expression in advanced disease, however only MAGE+/PD-L1- group was associated with shorter RFS (HR 1.89, 95%CI 1.19-2.99; p=0.006). MAGE+/PD-L1+ was associated with the worst PFS (HR 17.1, 95%CI 5.96-49.4; p=<0.001). MAGE-A expression was more prevalent high-grade (p=0.015), and higher stage ≥pT2 (p=0.001). The 5-year RFS in MAGE+ was 44%vs.58% for MAGE- samples. On multivariable analysis MP was also associated with shorter recurrence (HR 1.55, 95%CI 1.05-2.30; p=0.03). Similarly, MAGE+ was associated with shorter PFS (HR 3.12, 95%CI 1.12-8.68; p=0.03).

Conclusion: We report that the expression of MAGE-A and PD-L1 is increased in more advanced disease and associated with shorter PFS. Furthermore, expression of MAGE-A is significant in higher grade and stage, and was associated with shorter RFS and PFS. The finding of worse prognosis of MAGE-A/PD-L1 provides early evidence that a potential combinatorial treatment strategy of co-targeting MAGE/PD-L1 with respective agents might be feasible. Further studies are needed to validate these findings.

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