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

doi:10.1016/j.xgen.2023.100409

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. SolórzanoLindsay 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	100409
Journal	Cell Genomics
Volume	3
Issue number	10
DOIs	https://doi.org/10.1016/j.xgen.2023.100409
State	Published - Oct 11 2023

Keywords

aggressive thyroid cancer
anaplastic thyroid carcinoma
cancer-associated fibroblasts
molecular biomarkers
next-generation sequencing
tumor immune microenvironment

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Genetics

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10.1016/j.xgen.2023.100409

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Xu, G. J., Loberg, M. A., Gallant, J. N., Sheng, Q., Chen, S. C., Lehmann, B. D., Shaddy, S. M., Tigue, M. L., Phifer, C. J., Wang, L., Saab-Chalhoub, M. W., Dehan, L. M., Wei, Q., Chen, R., Li, B., Kim, C. Y., Ferguson, D. C., Netterville, J. L., Rohde, S. L., ... Weiss, V. L. (2023). Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction. Cell Genomics, 3(10), Article 100409. https://doi.org/10.1016/j.xgen.2023.100409

Xu, GJ, Loberg, MA, Gallant, JN, Sheng, Q, Chen, SC, Lehmann, BD, Shaddy, SM, Tigue, ML, Phifer, CJ, Wang, L, Saab-Chalhoub, MW, Dehan, LM, Wei, Q, Chen, R, Li, B, Kim, CY, Ferguson, DC, Netterville, JL, Rohde, SL, Solórzano, CC, Bischoff, LA, Baregamian, N, Shaver, AC, Mehrad, M, Ely, KA, Byrne, DW, Stricker, TP, Murphy, BA, Choe, JH, Kagohara, LT , Jaffee, EM, Huang, EC, Ye, F, Lee, E & Weiss, VL 2023, 'Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction', Cell Genomics, vol. 3, no. 10, 100409. https://doi.org/10.1016/j.xgen.2023.100409

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title = "Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction",

abstract = "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.",

keywords = "aggressive thyroid cancer, anaplastic thyroid carcinoma, cancer-associated fibroblasts, molecular biomarkers, next-generation sequencing, tumor immune microenvironment",

author = "Xu, {George J.} and Loberg, {Matthew A.} and Gallant, {Jean Nicolas} and Quanhu Sheng and Chen, {Sheau Chiann} and Lehmann, {Brian D.} and Shaddy, {Sophia M.} and Tigue, {Megan L.} and Phifer, {Courtney J.} and Li Wang and Saab-Chalhoub, {Mario W.} and Dehan, {Lauren M.} and Qiang Wei and Rui Chen and Bingshan Li and Kim, {Christine Y.} and Ferguson, {Donna C.} and Netterville, {James L.} and Rohde, {Sarah L.} and Sol{\'o}rzano, {Carmen C.} and Bischoff, {Lindsay A.} and Naira Baregamian and Shaver, {Aaron C.} and Mitra Mehrad and Ely, {Kim A.} and Byrne, {Daniel W.} and Stricker, {Thomas P.} and Murphy, {Barbara A.} and Choe, {Jennifer H.} and Kagohara, {Luciane T.} and Jaffee, {Elizabeth M.} and Huang, {Eric C.} and Fei Ye and Ethan Lee and Weiss, {Vivian L.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = oct,

day = "11",

doi = "10.1016/j.xgen.2023.100409",

language = "English (US)",

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T1 - Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction

AU - Xu, George J.

AU - Loberg, Matthew A.

AU - Gallant, Jean Nicolas

AU - Sheng, Quanhu

AU - Chen, Sheau Chiann

AU - Lehmann, Brian D.

AU - Shaddy, Sophia M.

AU - Tigue, Megan L.

AU - Phifer, Courtney J.

AU - Wang, Li

AU - Saab-Chalhoub, Mario W.

AU - Dehan, Lauren M.

AU - Wei, Qiang

AU - Chen, Rui

AU - Li, Bingshan

AU - Kim, Christine Y.

AU - Ferguson, Donna C.

AU - Netterville, James L.

AU - Rohde, Sarah L.

AU - Solórzano, Carmen C.

AU - Bischoff, Lindsay A.

AU - Baregamian, Naira

AU - Shaver, Aaron C.

AU - Mehrad, Mitra

AU - Ely, Kim A.

AU - Byrne, Daniel W.

AU - Stricker, Thomas P.

AU - Murphy, Barbara A.

AU - Choe, Jennifer H.

AU - Kagohara, Luciane T.

AU - Jaffee, Elizabeth M.

AU - Huang, Eric C.

AU - Ye, Fei

AU - Lee, Ethan

AU - Weiss, Vivian L.

PY - 2023/10/11

Y1 - 2023/10/11

N2 - 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.

AB - 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.

KW - aggressive thyroid cancer

KW - anaplastic thyroid carcinoma

KW - cancer-associated fibroblasts

KW - molecular biomarkers

KW - next-generation sequencing

KW - tumor immune microenvironment

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U2 - 10.1016/j.xgen.2023.100409

DO - 10.1016/j.xgen.2023.100409

M3 - Article

C2 - 37868034

AN - SCOPUS:85173169924

SN - 2666-979X

VL - 3

JO - Cell Genomics

JF - Cell Genomics

IS - 10

M1 - 100409

ER -

Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction

Abstract

Keywords

ASJC Scopus subject areas

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