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

被引：1740

作者：

Puram, Sidharth V. ^{[1
,2
,3
,4
,5
]}

Tirosh, Itay ^{[3
,6
]}

Parikh, Anuraag S. ^{[1
,2
,3
,4
,5
]}

Patel, Anoop P. ^{[1
,2
,3
,7
]}

Yizhak, Keren ^{[1
,2
,3
]}

Gillespie, Shawn ^{[1
,2
,3
]}

Rodman, Christopher ^{[3
]}

Luo, Christina L. ^{[1
,2
]}

Mroz, Edmund A. ^{[4
]}

Emerick, Kevin S. ^{[4
,5
]}

Deschler, Daniel G. ^{[4
,5
]}

Varvares, Mark A. ^{[4
,5
]}

Mylvaganam, Ravi ^{[1
,2
]}

Rozenblatt-Rosen, Orit ^{[3
]}

Rocco, James W. ^{[4
,5
,8
]}

Faquin, William C. ^{[1
,2
]}

Lin, Derrick T. ^{[4
,5
]}

Regev, Aviv ^{[3
,9
,10
,11
]}

Bernstein, Bradley E. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02114 USA

[3] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[4] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA

[5] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02115 USA

[6] Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel

[7] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA

[8] Ohio State Univ, Dept Otolaryngol, Columbus, OH 43210 USA

[9] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02142 USA

[10] MIT, Koch Inst, Cambridge, MA 02142 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL | 2017年 / 171卷 / 07期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; DNA-SEQUENCING DATA; RNA-SEQ; CARCINOMA; HETEROGENEITY; FRAMEWORK; GENOME; GLIOBLASTOMA; EXPRESSION; PLASTICITY;

D O I：

10.1016/j.cell.2017.10.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of similar to 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 sub-types 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.

引用

页码：1611 / +

页数：38

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