Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

Sidharth V. Puram; Itay Tirosh; Anuraag S. Parikh; Anoop P. Patel; Keren Yizhak; Shawn Gillespie; Christopher Rodman; Christina L. Luo; Edmund A. Mroz; Kevin S. Emerick; Daniel G. Deschler; Mark A. Varvares; Ravi Mylvaganam; Orit Rozenblatt-Rosen; James W. Rocco; William C. Faquin; Derrick T. Lin; Aviv Regev; Bradley E. Bernstein

doi:https://doi.org/10.1016/j.cell.2017.10.044

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

Sidharth V. Puram, Itay Tirosh, Anuraag S. Parikh, Anoop P. Patel, Keren Yizhak, Shawn Gillespie, Christopher Rodman, Christina L. Luo, Edmund A. Mroz, Kevin S. Emerick, Daniel G. Deschler, Mark A. Varvares, Ravi Mylvaganam, Orit Rozenblatt-Rosen, James W. Rocco, William C. Faquin, Derrick T. Lin, Aviv Regev, Bradley E. Bernstein

Department of Molecular Cell Biology

Weizmann Institute of Science

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

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.

Original language	English
Pages (from-to)	1611-1624.e24
Journal	Cell
Volume	171
Issue number	7
Early online date	30 Nov 2017
DOIs	https://doi.org/10.1016/j.cell.2017.10.044
State	Published - 14 Dec 2017

Keywords

epithelial-to-mesenchymal transition
head and neck squamous cell carcinoma
intra-tumoral heterogeneity
metastasis
scRNA-seq
single-cell RNA sequencing
tumor microenvironment

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Puram, S. V., Tirosh, I., Parikh, A. S., Patel, A. P., Yizhak, K., Gillespie, S., Rodman, C., Luo, C. L., Mroz, E. A., Emerick, K. S., Deschler, D. G., Varvares, M. A., Mylvaganam, R., Rozenblatt-Rosen, O., Rocco, J. W., Faquin, W. C., Lin, D. T., Regev, A., & Bernstein, B. E. (2017). Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer. Cell, 171(7), 1611-1624.e24. Advance online publication. https://doi.org/10.1016/j.cell.2017.10.044

@article{515d52f08924435a92973467f09c3664,

title = "Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer",

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 = "epithelial-to-mesenchymal transition, head and neck squamous cell carcinoma, intra-tumoral heterogeneity, metastasis, scRNA-seq, single-cell RNA sequencing, tumor microenvironment",

author = "Puram, {Sidharth V.} and Itay Tirosh and Parikh, {Anuraag S.} and Patel, {Anoop P.} and Keren Yizhak and Shawn Gillespie and Christopher Rodman and Luo, {Christina L.} and Mroz, {Edmund A.} and Emerick, {Kevin S.} and Deschler, {Daniel G.} and Varvares, {Mark A.} and Ravi Mylvaganam and Orit Rozenblatt-Rosen and Rocco, {James W.} and Faquin, {William C.} and Lin, {Derrick T.} and Aviv Regev and Bernstein, {Bradley E.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = dec,

day = "14",

doi = "https://doi.org/10.1016/j.cell.2017.10.044",

language = "الإنجليزيّة",

volume = "171",

pages = "1611--1624.e24",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "7",

}

Puram, SV, Tirosh, I, Parikh, AS, Patel, AP, Yizhak, K, Gillespie, S, Rodman, C, Luo, CL, Mroz, EA, Emerick, KS, Deschler, DG, Varvares, MA, Mylvaganam, R, Rozenblatt-Rosen, O, Rocco, JW, Faquin, WC, Lin, DT, Regev, A & Bernstein, BE 2017, 'Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer', Cell, vol. 171, no. 7, pp. 1611-1624.e24. https://doi.org/10.1016/j.cell.2017.10.044

TY - JOUR

T1 - Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

AU - Puram, Sidharth V.

AU - Tirosh, Itay

AU - Parikh, Anuraag S.

AU - Patel, Anoop P.

AU - Yizhak, Keren

AU - Gillespie, Shawn

AU - Rodman, Christopher

AU - Luo, Christina L.

AU - Mroz, Edmund A.

AU - Emerick, Kevin S.

AU - Deschler, Daniel G.

AU - Varvares, Mark A.

AU - Mylvaganam, Ravi

AU - Rozenblatt-Rosen, Orit

AU - Rocco, James W.

AU - Faquin, William C.

AU - Lin, Derrick T.

AU - Regev, Aviv

AU - Bernstein, Bradley E.

PY - 2017/12/14

Y1 - 2017/12/14

N2 - 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.

AB - 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.

KW - epithelial-to-mesenchymal transition

KW - head and neck squamous cell carcinoma

KW - intra-tumoral heterogeneity

KW - metastasis

KW - scRNA-seq

KW - single-cell RNA sequencing

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85035813065&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.cell.2017.10.044

DO - https://doi.org/10.1016/j.cell.2017.10.044

M3 - مقالة

C2 - 29198524

SN - 0092-8674

VL - 171

SP - 1611-1624.e24

JO - Cell

JF - Cell

IS - 7

ER -

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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