PD-L1 expression is regulated by microphthalmia- associated transcription factor (MITF) in nodular melanoma
| Autor: | Damir Vučinić, Gordana Zamolo, Blaženka Grahovac, Bojana Mohar Vitezić, Leo Kovač, Margita Belušić-Gobić, Maja Grahovac |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Microphthalmia-Associated Transcription Factor
Skin Neoplasms integumentary system Melanoma Cell Biology Biology Cell cycle PD-L1 Malignant melanoma medicine.disease Microphthalmia-associated transcription factor Nodular melanoma B7-H1 Antigen Pathology and Forensic Medicine Gene Expression Regulation Neoplastic Cyclin D1 Proto-Oncogene Proteins c-bcl-2 CCND1 Gene Amplification Gene duplication medicine Cancer research Humans Transcription factor Retrospective Studies |
| Popis: | Malignant melanoma (MM) is known to avoid the host’s immune response. Studies on in vitro melanoma cell lines link the microphthalmia-associated transcription factor (MITF) with the regulation of the PD-L1 expression. It seems that MITF affects the activation of the gene responsible for PD-L1 protein expression. Several proteins, including Bcl-2 and Cyclin D1, play major roles in malignant melanoma cell cycle regulation and survival. Our study aims to assess the relationship between MITF, Bcl-2, and cyclin D1 protein expression and the expression of the PD-L1 molecule. Additionally, we examined the association of BRAF mutation, MITF, and CCND1 gene amplification with PD-L1 protein expression. We performed immunohistochemical staining on fifty-two tumour samples from patients diagnosed with nodular melanoma (NM). BRAF V600 mutation, MITF, and CCND1 gene amplification analyses were analyzed by the Sanger sequencing and QRT-PCR methods, respectively. Statistical analyses confirmed the significant inverse correlation between cyclin D1 and PD-L1 expression (p= 0.001) and correlation between PD-L1 and MITF protein expression (p=0.023). We found a statistically significant inverse correlation between the present MITF gene amplification and PD-L1 (p=0.007) and MITF protein expression (p=3.4×10-6), respectively. Our study, performed on clinical NM materials, supports the in vitro study findings providing a rationale for the potential MITF-dependent regulation of PD-L1 expression in malignant melanoma. |
| Databáze: | OpenAIRE |
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