Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma
| Autor: | Karim Chamie, Rajul K. Jain, Allan J. Pantuck, Alexandra Drakaki, Stephanie H. Astrow, Arie S. Belldegrun, Izak Faiena, David Elashoff, Adrian Bot |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Male endocrine system Cancer Research medicine.medical_specialty Urologic Neoplasms Immunology Disease B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Biomarkers Tumor Immunology and Allergy Humans Stage (cooking) neoplasms Melanoma Urothelial carcinoma Aged Neoplasm Staging Proportional Hazards Models Melanoma-associated antigen Tissue microarray business.industry Hazard ratio Middle Aged Prognosis Survival Analysis Confidence interval Gene Expression Regulation Neoplastic Exact test Female business Melanoma-Specific Antigens 030215 immunology |
| Zdroj: | Cancer immunology, immunotherapy : CII. 68(5) |
| ISSN: | 1432-0851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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