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Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring

OBJECTIVE: The significant metastatic potential of uveal melanoma (UVM) lends to high mortality. Even with successful local tumor treatment, many patients will develop metastatic disease. The present study aims to elucidate the relationship between tumor-infiltrating immune cell (TIIC) diversity and...

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Autores principales: Diaz, Michael Joseph, Fadil, Angela, Kleinberg, Giona, Root, Kevin T, Ladehoff, Lauren, Batchu, Sai, Lucke-Wold, Brandon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977264/
https://www.ncbi.nlm.nih.gov/pubmed/36866123
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author Diaz, Michael Joseph
Fadil, Angela
Kleinberg, Giona
Root, Kevin T
Ladehoff, Lauren
Batchu, Sai
Lucke-Wold, Brandon
author_facet Diaz, Michael Joseph
Fadil, Angela
Kleinberg, Giona
Root, Kevin T
Ladehoff, Lauren
Batchu, Sai
Lucke-Wold, Brandon
author_sort Diaz, Michael Joseph
collection PubMed
description OBJECTIVE: The significant metastatic potential of uveal melanoma (UVM) lends to high mortality. Even with successful local tumor treatment, many patients will develop metastatic disease. The present study aims to elucidate the relationship between tumor-infiltrating immune cell (TIIC) diversity and survival to identify potential therapeutic targets and improve UVM prognosis. METHODS: Bulk deconvolution was used to determine the relative proportions of 22 hematopoietic TIIC from 80 UVM tumor samples. Cytolytic activity (CYT) was determined, and associated survival probabilities were mined using time-to-event data. Nominal P-values were subjected to FDR correction. RESULTS: High relative abundance of tumor-infiltrating naïve B cells, resting memory CD4(+) T cells, and monocytes correlated with better overall and disease-free survival probability. Low relative abundance of CD8(+) T cells correlated with better overall survival and disease-free survival probability. CYT correlated positively with relative abundance of naïve B cells, resting memory CD4(+) T cells, and monocytes. CYT correlated negatively with relative abundance of CD8(+) T cells. CONCLUSION: Infiltrating naïve B cells, resting memory CD4(+) T cells, monocytes, and CD8(+) T cells are potential therapeutic targets in UVM that warrant further investigation. High CYT estimates associate with worse UVM survival outcomes.
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spelling pubmed-99772642023-03-01 Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring Diaz, Michael Joseph Fadil, Angela Kleinberg, Giona Root, Kevin T Ladehoff, Lauren Batchu, Sai Lucke-Wold, Brandon Neurosci Chron Article OBJECTIVE: The significant metastatic potential of uveal melanoma (UVM) lends to high mortality. Even with successful local tumor treatment, many patients will develop metastatic disease. The present study aims to elucidate the relationship between tumor-infiltrating immune cell (TIIC) diversity and survival to identify potential therapeutic targets and improve UVM prognosis. METHODS: Bulk deconvolution was used to determine the relative proportions of 22 hematopoietic TIIC from 80 UVM tumor samples. Cytolytic activity (CYT) was determined, and associated survival probabilities were mined using time-to-event data. Nominal P-values were subjected to FDR correction. RESULTS: High relative abundance of tumor-infiltrating naïve B cells, resting memory CD4(+) T cells, and monocytes correlated with better overall and disease-free survival probability. Low relative abundance of CD8(+) T cells correlated with better overall survival and disease-free survival probability. CYT correlated positively with relative abundance of naïve B cells, resting memory CD4(+) T cells, and monocytes. CYT correlated negatively with relative abundance of CD8(+) T cells. CONCLUSION: Infiltrating naïve B cells, resting memory CD4(+) T cells, monocytes, and CD8(+) T cells are potential therapeutic targets in UVM that warrant further investigation. High CYT estimates associate with worse UVM survival outcomes. 2022 /pmc/articles/PMC9977264/ /pubmed/36866123 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Diaz, Michael Joseph
Fadil, Angela
Kleinberg, Giona
Root, Kevin T
Ladehoff, Lauren
Batchu, Sai
Lucke-Wold, Brandon
Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title_full Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title_fullStr Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title_full_unstemmed Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title_short Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
title_sort omics analysis of uveal melanoma: leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977264/
https://www.ncbi.nlm.nih.gov/pubmed/36866123
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