The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets

Zhongyi Hu; Jiao Yuan; Meixiao Long; Junjie Jiang; Youyou Zhang; Tianli Zhang; Mu Xu; Yi Fan; Janos L Tanyi; Kathleen T Montone; Omid Tavana; Ho Man Chan; Xiaowen Hu; Robert H Vonderheide; Lin Zhang

doi:10.1038/s43018-021-00282-w

The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets

Nat Cancer. 2021 Dec;2(12):1406-1422. doi: 10.1038/s43018-021-00282-w. Epub 2021 Dec 13.

Authors

Zhongyi Hu^#^{1

2}, Jiao Yuan^#^{1

2}, Meixiao Long³, Junjie Jiang^{1

2}, Youyou Zhang^{1

2}, Tianli Zhang¹, Mu Xu¹, Yi Fan⁴, Janos L Tanyi², Kathleen T Montone⁵, Omid Tavana⁶, Ho Man Chan⁶, Xiaowen Hu^{7

8}, Robert H Vonderheide⁹, Lin Zhang^{10

11

12}

Affiliations

¹ Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA.
³ Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, OH, USA.
⁴ Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Waltham, MA, USA.
⁷ Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA, USA. xiaowenh@upenn.edu.
⁸ Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. xiaowenh@upenn.edu.
⁹ Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. rhv@upenn.edu.
¹⁰ Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA, USA. linzhang@upenn.edu.
¹¹ Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. linzhang@upenn.edu.
¹² Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. linzhang@upenn.edu.

^# Contributed equally.

Abstract

Cell-surface proteins (SPs) are a rich source of immune and targeted therapies. By systematically integrating single-cell and bulk genomics, functional studies and target actionability, in the present study we comprehensively identify and annotate genes encoding SPs (GESPs) pan-cancer. We characterize GESP expression patterns, recurrent genomic alterations, essentiality, receptor-ligand interactions and therapeutic potential. We also find that mRNA expression of GESPs is cancer-type specific and positively correlates with protein expression, and that certain GESP subgroups function as common or specific essential genes for tumor cell growth. We also predict receptor-ligand interactions substantially deregulated in cancer and, using systems biology approaches, we identify cancer-specific GESPs with therapeutic potential. We have made this resource available through the Cancer Surfaceome Atlas ( http://fcgportal.org/TCSA ) within the Functional Cancer Genome data portal.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Genome
Genomics*
Humans
Ligands
Neoplasms* / drug therapy
Proteomics

Substances

Ligands

Abstract

Publication types

MeSH terms

Substances

Grants and funding