Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer
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Author(s)
Puram, Sidharth V.
Tirosh, Itay
Parikh, Anuraag S.
Patel, Anoop P.
Yizhak, Keren
Gillespie, Shawn
Rodman, Christopher
Luo, Christina L.
Mroz, Edmund A.
Emerick, Kevin S.
Date Issued
November 2017
Journal
Cell
Publisher
Elsevier
Citation
Puram, Sidharth V. et al. “Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.” Cell 171, 7 (December 2017): 1611–1624 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis. Single-cell transcriptomic analysis in patients with head and neck squamous cell carcinoma highlights the heterogeneous composition of malignant and non-malignant cells in the tumor microenvironment and associates a partial EMT program with metastasis. Keywords: single-cell RNA sequencing; metastasis; head and neck squamous cell carcinoma; epithelial-to-mesenchymal transition; tumor microenvironment; scRNA-seq; intra-tumoral heterogeneity
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2017.10.044
