Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers
| العنوان: | Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers |
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| المؤلفون: | Jack S Crabb, Bo Hu, Geeng-Fu Jang, Belinda Willard, Sarah E. Coupland, Helen Kalirai, Arun D. Singh, John W. Crabb |
| المصدر: | Cancers CANCERS Volume 13 Issue 14 Cancers, Vol 13, Iss 3520, p 3520 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, quantitative proteomics, Cancer Research, Quantitative proteomics, Proteomics, Article, CDH1, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, metastasis, RC254-282, prediction modeling, biology, Melanoma, immune profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, bioinformatics, medicine.disease, Immune checkpoint, 030104 developmental biology, Oncology, iTRAQ, 030220 oncology & carcinogenesis, Proteome, biology.protein, Cancer research, uveal melanoma |
| الوصف: | Simple Summary This study pursued the proteomic analysis of primary uveal melanoma (pUM) for insights into the mechanisms of metastasis and protein biomarkers. Liquid chromatography tandem mass spectrometry quantitative proteomic technology was used to analyze 53 metastasizing and 47 non-metastasizing pUM. The determined proteome of 3935 proteins was very similar between the metastasizing and non-metastasizing pUM, but included the identification of 402 differentially expressed (DE) proteins. Bioinformatic analyses suggest significant differences in the immune response between metastasizing and non-metastasizing pUM. Immune protein profiling results were consistent with transcriptomic studies, showing the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as potential targets for immune therapy checkpoint blockade. Prediction modeling of the proteomic data identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy. Abstract Uveal melanoma metastases are lethal and remain incurable. A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM proteins relative to the normal choroid excised from UM donor eyes. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM (n = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune proteins (n = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as possible candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for protein-based prognostic methods for detecting UM metastasis. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e143cc3c26f5f1559da0547ab975103b https://pubmed.ncbi.nlm.nih.gov/34298739 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e143cc3c26f5f1559da0547ab975103b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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