Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction

• DOI: 10.1016/j.xgen.2023.100409
• Publication Date: 2023-09-15T10:49:08Z
• Authors: 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-Cha...; 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
• Keywords: tumor immune microenvironment; anaplastic thyroid carcinoma; Genetics; next-generation sequencing; aggressive thyroid cancer; QH426-470; cancer-associated fibroblasts; Internal medicine; RC31-1245; molecular biomarkers; Article; 3. Good health

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging histology, with few molecular prognostic treatment biomarkers. Here, we utilize a large cohort 251 patients 312 samples from two tertiary medical centers perform DNA/RNA sequencing, spatial transcriptomics, multiplex immunofluorescence to identify biomarkers aggressive malignancy. We high-risk mutations discover unique signature disease, the Molecular Aggression Prediction (MAP) score, which provides improved prognostication over alone. The MAP score enriched for genes involved in epithelial de-differentiation, cellular division, tumor microenvironment. also identifies tumors lymphocyte-rich stroma that may benefit immunotherapy. Future clinical profiling stromal microenvironment could improve prognostication, inform immunotherapy, support development novel therapeutics other stroma-rich