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Prognostic significance of CD200 expression and correlation with COX-2 expression in cutaneous melanoma

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Abstract
Background: Immune escape by tumors can occur by various mechanisms. As immunotherapy targeting immune checkpoints such as Cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1 is considered as a good alternative to conventional chemotherapy in melanoma patients, more research on new immune checkpoints, which allows better therapeutic efficacy with less toxicity is needed.
Objective: We evaluated CD200 and COX-2 expression in melanoma and their correlation, and determined their effects on clinicopathological characteristics including survival data.
Method: Tumor samples obtained from primary melanoma lesions were analyzed for both CD200 and COX-2 expression by IHC analysis. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAFV600E A375 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of CD200 in vitro. Tissue specimens from 118 patients of melanoma were evaluated by immunohistochemistry for CD200 and COX-2 expression. Clinidopathological features including survival data were analyzed according to the expression of CD200 and COX-2.
Results: CD200 and COX-2 were positive in 47.4% and 48.3% of melanoma patients. Both showed a tendency to be associated with aggressive clinicopathologic features. CD200 expression positively correlated with COX-2 expression in human melanoma cells. CD200 and COX-2 expression in melanoma were independent prognostic markers for worse overall survival. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of CD200 in BRAFV600E melanoma cell lines.
Limitations: Status of BRAF and NRAS mutations was not analyzed in melanoma patients. We could not investigate the difference according to the subtype of melanoma.
Conclusion: Our study suggests that CD200 expression by melanoma cells is associated with more aggressive pathologic features and worse survival data. Anti-CD200 treatment might be therapeutically beneficial for melanoma treatment.
Author(s)
이미혜
Issued Date
2018
Awarded Date
2019-02
Type
Dissertation
Keyword
CD200Tumor microenvironmentimmune checkpointMelanoma
URI
https://oak.ulsan.ac.kr/handle/2021.oak/6283
http://ulsan.dcollection.net/common/orgView/200000176968
Alternative Author(s)
Lee Mihye
Affiliation
울산대학교
Department
일반대학원 의학과
Advisor
Jee Ho Choi
Degree
Doctor
Publisher
울산대학교 일반대학원 의학과
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medicine > 2. Theses (Ph.D)
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