公开(公告)号：US20200071773A1

公开(公告)日：2020-03-05

申请号：US16604651

申请日：2018-04-12

申请人： Massachusetts Eye and Ear Infirmary ,  The General Hospital Corporation ,  The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Sidharth Puram ,  Itay Tirosh ,  Anuraag Parikh ,  Derrick Lin ,  Aviv Regev ,  Bradley Bernstein

IPC分类号： C12Q1/6886 ,  A61P35/04 ,  C12Q1/6837 ,  G16B25/10 ,  G16B40/00

摘要： The present invention advantageously provides for novel gene signatures, tools and methods for the treatment and prognosis of epithelial tumors. Applicants have used single cell RNA-seq to reveal novel expression programs of malignant, stromal and immune cells in the HNSCC tumor ecosystem. Malignant cells varied in expression of programs related to stress, hypoxia and epithelial differentiation. A partial EMT-like program (p-EMT) was discovered that was expressed in cells residing at the leading edge of tumors. Applicants unexpectedly linked the p-EMT state to metastasis and adverse clinical features that may be used to direct treatment of epithelial cancers (e.g., HNSCC). Applicants also show that metastases are dynamically regulated by the tumor microenvironment (TME). Finally, a computational modeling approach was developed that allows analysis of malignant cells in bulk sequencing samples.