Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Autor:	Xu GJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Loberg MA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Gallant JN; Department of Otolaryngology - Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Sheng Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Chen SC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Lehmann BD; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Shaddy SM; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA., Tigue ML; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Phifer CJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Wang L; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Saab-Chalhoub MW; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Dehan LM; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Wei Q; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Chen R; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Li B; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Kim CY; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Ferguson DC; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Netterville JL; Department of Otolaryngology - Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Rohde SL; Department of Otolaryngology - Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Solórzano CC; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Bischoff LA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Baregamian N; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Shaver AC; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Mehrad M; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Ely KA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Byrne DW; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Stricker TP; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Murphy BA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Choe JH; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Kagohara LT; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg-Kimmel Immunotherapy Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Jaffee EM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg-Kimmel Immunotherapy Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Huang EC; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA., Ye F; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Lee E; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA., Weiss VL; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2023 Sep 14; Vol. 3 (10), pp. 100409. Date of Electronic Publication: 2023 Sep 14 (Print Publication: 2023).
DOI:	10.1016/j.xgen.2023.100409
Abstrakt:	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. Competing Interests: E.L. is a co-founder of StemSynergy Therapeutics, a company that seeks to develop inhibitors of major signaling pathways (including the Wnt pathway) for the treatment of cancer. E.M.J. reports other support from Abmeta, other support from Adventris, personal fees from Achilles, personal fees from DragonFly, personal fees from Parker Institute, personal fees from Surge, grants from Lustgarten, grants from Genentech, personal fees from Mestag, personal fees from Medical Home Group, grants from BMS, and grants from Break Through Cancer outside the submitted work. (© 2023 The Author(s).)
Databáze:	MEDLINE
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