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Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction
Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary me...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589635/ https://www.ncbi.nlm.nih.gov/pubmed/37868034 http://dx.doi.org/10.1016/j.xgen.2023.100409 |
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author | Xu, George J. Loberg, Matthew A. Gallant, Jean-Nicolas Sheng, Quanhu Chen, Sheau-Chiann Lehmann, Brian D. Shaddy, Sophia M. Tigue, Megan L. Phifer, Courtney J. Wang, Li Saab-Chalhoub, Mario W. Dehan, Lauren M. Wei, Qiang Chen, Rui Li, Bingshan Kim, Christine Y. Ferguson, Donna C. Netterville, James L. Rohde, Sarah L. Solórzano, Carmen C. Bischoff, Lindsay A. Baregamian, Naira Shaver, Aaron C. Mehrad, Mitra Ely, Kim A. Byrne, Daniel W. Stricker, Thomas P. Murphy, Barbara A. Choe, Jennifer H. Kagohara, Luciane T. Jaffee, Elizabeth M. Huang, Eric C. Ye, Fei Lee, Ethan Weiss, Vivian L. |
author_facet | Xu, George J. Loberg, Matthew A. Gallant, Jean-Nicolas Sheng, Quanhu Chen, Sheau-Chiann Lehmann, Brian D. Shaddy, Sophia M. Tigue, Megan L. Phifer, Courtney J. Wang, Li Saab-Chalhoub, Mario W. Dehan, Lauren M. Wei, Qiang Chen, Rui Li, Bingshan Kim, Christine Y. Ferguson, Donna C. Netterville, James L. Rohde, Sarah L. Solórzano, Carmen C. Bischoff, Lindsay A. Baregamian, Naira Shaver, Aaron C. Mehrad, Mitra Ely, Kim A. Byrne, Daniel W. Stricker, Thomas P. Murphy, Barbara A. Choe, Jennifer H. Kagohara, Luciane T. Jaffee, Elizabeth M. Huang, Eric C. Ye, Fei Lee, Ethan Weiss, Vivian L. |
author_sort | Xu, George J. |
collection | PubMed |
description | Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors. |
format | Online Article Text |
id | pubmed-10589635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105896352023-10-22 Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction Xu, George J. Loberg, Matthew A. Gallant, Jean-Nicolas Sheng, Quanhu Chen, Sheau-Chiann Lehmann, Brian D. Shaddy, Sophia M. Tigue, Megan L. Phifer, Courtney J. Wang, Li Saab-Chalhoub, Mario W. Dehan, Lauren M. Wei, Qiang Chen, Rui Li, Bingshan Kim, Christine Y. Ferguson, Donna C. Netterville, James L. Rohde, Sarah L. Solórzano, Carmen C. Bischoff, Lindsay A. Baregamian, Naira Shaver, Aaron C. Mehrad, Mitra Ely, Kim A. Byrne, Daniel W. Stricker, Thomas P. Murphy, Barbara A. Choe, Jennifer H. Kagohara, Luciane T. Jaffee, Elizabeth M. Huang, Eric C. Ye, Fei Lee, Ethan Weiss, Vivian L. Cell Genom Article Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors. Elsevier 2023-09-14 /pmc/articles/PMC10589635/ /pubmed/37868034 http://dx.doi.org/10.1016/j.xgen.2023.100409 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Xu, George J. Loberg, Matthew A. Gallant, Jean-Nicolas Sheng, Quanhu Chen, Sheau-Chiann Lehmann, Brian D. Shaddy, Sophia M. Tigue, Megan L. Phifer, Courtney J. Wang, Li Saab-Chalhoub, Mario W. Dehan, Lauren M. Wei, Qiang Chen, Rui Li, Bingshan Kim, Christine Y. Ferguson, Donna C. Netterville, James L. Rohde, Sarah L. Solórzano, Carmen C. Bischoff, Lindsay A. Baregamian, Naira Shaver, Aaron C. Mehrad, Mitra Ely, Kim A. Byrne, Daniel W. Stricker, Thomas P. Murphy, Barbara A. Choe, Jennifer H. Kagohara, Luciane T. Jaffee, Elizabeth M. Huang, Eric C. Ye, Fei Lee, Ethan Weiss, Vivian L. Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title | Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title_full | Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title_fullStr | Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title_full_unstemmed | Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title_short | Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
title_sort | molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589635/ https://www.ncbi.nlm.nih.gov/pubmed/37868034 http://dx.doi.org/10.1016/j.xgen.2023.100409 |
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