title: Integrated omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact.
abstract: Cancer results from processes prone to selective pressure and dysregulation acting along the sequence-to-phenotype continuum DNA → RNA → protein → disease. However, the extent to which cancer is a manifestation of the proteome is unknown. Here we present an integrated omic map representing non-small cell lung carcinoma. Dysregulated proteins not previously implicated as cancer drivers are encoded throughout the genome including, but not limited to, regions of recurrent DNA amplification/deletion. Clustering reveals signatures composed of metabolism proteins particularly highly recapitulated between patient-matched primary and xenograft tumours. Interrogation of The Cancer Genome Atlas reveals cohorts of patients with lung and other cancers that have DNA alterations in genes encoding the signatures, and this was accompanied by differences in survival. The recognition of genome and proteome alterations as related products of selective pressure driving the disease phenotype may be a general approach to uncover and group together cryptic, polygenic disease drivers.
authors.affiliation: Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Christine
authors.initials: C
authors.lastname: To
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Zhu
authors.affiliation: Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4.
authors.forename: Jiefei
authors.initials: J
authors.lastname: Tong
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Nhu-An
authors.initials: NA
authors.lastname: Pham
authors.affiliation: Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4.
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ignatchenko
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Alex
authors.initials: A
authors.lastname: Ignatchenko
authors.affiliation: 1] Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4 [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wang
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.affiliation: Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 1] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] The Dalla Lana School of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada M5T 3MT.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: 1] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: 1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7 [2] Ontario Institute for Cancer Research, 661 University Avenue, Toronto, Ontario, Canada M5G 0A3.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Muthuswamy
authors.affiliation: 1] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: 1] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7 [3] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Ming Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: 1] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.affiliation: 1] Department of Molecular Structure and Function, The Hospital For Sick Children, 686 Bay Street, Toronto, Ontario, Canada M5G0A4 [2] Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Moran
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D004247:DNA / Q000032:analysis*; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D012313:RNA / Q000032:analysis*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D020543:Proteome; D012313:RNA; D004247:DNA