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PMID: 26193342 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The prognostic landscape of genes and infiltrating immune cells across human cancers.

Nature medicine ·Vol. 21 ·No. 8 ·2015-08-00 ·Pages 938-945

Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD, Diehn M, West RB, Plevritis SK, Alizadeh AA

Abstract

Molecular profiles of tumors and tumor-associated cells hold great promise as biomarkers of clinical outcomes. However, existing data sets are fragmented and difficult to analyze systematically. Here we present a pan-cancer resource and meta-analysis of expression signatures from ∼18,000 human tumors with overall survival outcomes across 39 malignancies. By using this resource, we identified a forkhead box MI (FOXM1) regulatory network as a major predictor of adverse outcomes, and we found that expression of favorably prognostic genes, including KLRB1 (encoding CD161), largely reflect tumor-associated leukocytes. By applying CIBERSORT, a computational approach for inferring leukocyte representation in bulk tumor transcriptomes, we identified complex associations between 22 distinct leukocyte subsets and cancer survival. For example, tumor-associated neutrophil and plasma cell signatures emerged as significant but opposite predictors of survival for diverse solid tumors, including breast and lung adenocarcinomas. This resource and associated analytical tools (http://precog.stanford.edu) may help delineate prognostic genes and leukocyte subsets within and across cancers, shed light on the impact of tumor heterogeneity on cancer outcomes, and facilitate the discovery of biomarkers and therapeutic targets.

MeSH Terms
Humans Lymphocytes, Tumor-Infiltrating/physiology Neoplasms/genetics,immunology,mortality Neutrophil Infiltration Plasma Cells/physiology Prognosis
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Gentles Andrew J
Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA. | Department of Radiology, Stanford University, Stanford, California, USA.
Newman Aaron M
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
Liu Chih Long
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
Bratman Scott V
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Radiation Oncology, Stanford University, Stanford, California, USA.
Feng Weiguo
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Radiation Oncology, Stanford University, Stanford, California, USA.
Kim Dongkyoon
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
Nair Viswam S
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California, USA.
Xu Yue
Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
Khuong Amanda
Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
Hoang Chuong D
Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
Diehn Maximilian
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Radiation Oncology, Stanford University, Stanford, California, USA. | Stanford Cancer Institute, Stanford University, Stanford, California, USA.
West Robert B
Department of Pathology, Stanford University, Stanford, California, USA.
Plevritis Sylvia K
Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA. | Department of Radiology, Stanford University, Stanford, California, USA.
Alizadeh Ash A
Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA. | Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. | Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, California, USA. | Stanford Cancer Institute, Stanford University, Stanford, California, USA. | Department of Medicine, Division of Hematology, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.3909
Published
2015-08-00
Epub
2015-00-20
Pages
938-945
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC4852857
Subset
IM
Grants
NCI NIH HHS · T32 CA009302 · United States
NCI NIH HHS · U01CA154969 · United States
NCI NIH HHS · 5T32 CA09302-35 · United States
NCI NIH HHS · U01 CA194389 · United States
NCI NIH HHS · U01 CA154969 · United States
NCI NIH HHS · U54 CA149145 · United States
NCI NIH HHS · R01 CA188298 · United States
External Links
PubMed source DOI: 10.1038/nm.3909 PMC Full Text View journal details
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