Cell Genomics (Oct 2023)
Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction
- George J. Xu,
- Matthew A. Loberg,
- Jean-Nicolas Gallant,
- Quanhu Sheng,
- Sheau-Chiann Chen,
- Brian D. Lehmann,
- Sophia M. Shaddy,
- Megan L. Tigue,
- Courtney J. Phifer,
- Li Wang,
- Mario W. Saab-Chalhoub,
- Lauren M. Dehan,
- Qiang Wei,
- Rui Chen,
- Bingshan Li,
- Christine Y. Kim,
- Donna C. Ferguson,
- James L. Netterville,
- Sarah L. Rohde,
- Carmen C. Solórzano,
- Lindsay A. Bischoff,
- Naira Baregamian,
- Aaron C. Shaver,
- Mitra Mehrad,
- Kim A. Ely,
- Daniel W. Byrne,
- Thomas P. Stricker,
- Barbara A. Murphy,
- Jennifer H. Choe,
- Luciane T. Kagohara,
- Elizabeth M. Jaffee,
- Eric C. Huang,
- Fei Ye,
- Ethan Lee,
- Vivian L. Weiss
Affiliations
- George J. Xu
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Matthew A. Loberg
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Jean-Nicolas Gallant
- Department of Otolaryngology – Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
- Quanhu Sheng
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Sheau-Chiann Chen
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Brian D. Lehmann
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Sophia M. Shaddy
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Megan L. Tigue
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Courtney J. Phifer
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Li Wang
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Mario W. Saab-Chalhoub
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Lauren M. Dehan
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Qiang Wei
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
- Rui Chen
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
- Bingshan Li
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
- Christine Y. Kim
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Donna C. Ferguson
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- James L. Netterville
- Department of Otolaryngology – Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
- Sarah L. Rohde
- Department of Otolaryngology – Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
- Carmen C. Solórzano
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
- Lindsay A. Bischoff
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Naira Baregamian
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
- Aaron C. Shaver
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Mitra Mehrad
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Kim A. Ely
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Daniel W. Byrne
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Thomas P. Stricker
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Barbara A. Murphy
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Jennifer H. Choe
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Luciane T. Kagohara
- 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
- Elizabeth M. Jaffee
- 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
- Eric C. Huang
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Fei Ye
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Ethan Lee
- 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
- Vivian L. Weiss
- 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; Corresponding author
- Journal volume & issue
-
Vol. 3,
no. 10
p. 100409
Abstract
Summary: 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.
