Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer
Objective: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/6/885 |
| _version_ | 1797593907219922944 |
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| author | Zin W. Myint Zena Chahine Rani Jayswal Emily Bachert Robert J. McDonald Stephen E. Strup Andrew C. James Patrick J. Hensley Derek B. Allison |
| author_facet | Zin W. Myint Zena Chahine Rani Jayswal Emily Bachert Robert J. McDonald Stephen E. Strup Andrew C. James Patrick J. Hensley Derek B. Allison |
| author_sort | Zin W. Myint |
| collection | DOAJ |
| description | Objective: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. Materials and Methods: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson’s chi-squared tests and the Kaplan–Meier method, respectively. Results: A total of 87 MIBC patients were included. The median age was 66 (39–84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2–14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (<i>p</i> = 0.006), non-responders (<i>p</i> = 0.002), and at stage ≥ 3 (<i>p</i> < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. Conclusion: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC. |
| first_indexed | 2024-03-11T02:16:08Z |
| format | Article |
| id | doaj.art-2091118ebbd2482980af7db47a5aa19f |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T02:16:08Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-2091118ebbd2482980af7db47a5aa19f2023-11-18T11:10:04ZengMDPI AGJournal of Personalized Medicine2075-44262023-05-0113688510.3390/jpm13060885Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder CancerZin W. Myint0Zena Chahine1Rani Jayswal2Emily Bachert3Robert J. McDonald4Stephen E. Strup5Andrew C. James6Patrick J. Hensley7Derek B. Allison8Division of Medical Oncology, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USADivision of Medical Oncology, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USADepartment of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USAObjective: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. Materials and Methods: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson’s chi-squared tests and the Kaplan–Meier method, respectively. Results: A total of 87 MIBC patients were included. The median age was 66 (39–84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2–14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (<i>p</i> = 0.006), non-responders (<i>p</i> = 0.002), and at stage ≥ 3 (<i>p</i> < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. Conclusion: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.https://www.mdpi.com/2075-4426/13/6/885muscle invasive bladder cancerCD47 expressionneoadjuvant therapybiomarker |
| spellingShingle | Zin W. Myint Zena Chahine Rani Jayswal Emily Bachert Robert J. McDonald Stephen E. Strup Andrew C. James Patrick J. Hensley Derek B. Allison Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer Journal of Personalized Medicine muscle invasive bladder cancer CD47 expression neoadjuvant therapy biomarker |
| title | Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer |
| title_full | Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer |
| title_fullStr | Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer |
| title_full_unstemmed | Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer |
| title_short | Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer |
| title_sort | association of cd47 expression with clinicopathologic characteristics and survival outcomes in muscle invasive bladder cancer |
| topic | muscle invasive bladder cancer CD47 expression neoadjuvant therapy biomarker |
| url | https://www.mdpi.com/2075-4426/13/6/885 |
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