title: The prognostic landscape of genes and infiltrating immune cells across human cancers.
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.
authors.affiliation: Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA.|Department of Radiology, Stanford University, Stanford, California, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gentles
authors.affiliation: 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.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Newman
authors.affiliation: 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.
authors.forename: Chih Long
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Radiation Oncology, Stanford University, Stanford, California, USA.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Bratman
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Radiation Oncology, Stanford University, Stanford, California, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Feng
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
authors.forename: Dongkyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California, USA.
authors.forename: Viswam S
authors.initials: VS
authors.lastname: Nair
authors.affiliation: Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Khuong
authors.affiliation: Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, Stanford, California, USA.
authors.forename: Chuong D
authors.initials: CD
authors.lastname: Hoang
authors.affiliation: 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.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.affiliation: Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA.|Department of Radiology, Stanford University, Stanford, California, USA.
authors.forename: Sylvia K
authors.initials: SK
authors.lastname: Plevritis
authors.affiliation: 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.
authors.forename: Ash A
authors.initials: AA
authors.lastname: Alizadeh
mesh_terms: D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality*; D020556:Neutrophil Infiltration; D010950:Plasma Cells / Q000502:physiology; D011379:Prognosis