title: The lung-specific proteome defined by integration of transcriptomics and antibody-based profiling.
abstract: The combined action of multiple cell types is essential for the physiological function of the lung, and increased awareness of the molecular constituents characterizing each cell type is likely to advance the understanding of lung biology and disease. In the current study, we used genome-wide RNA sequencing of normal lung parenchyma and 26 additional tissue types, combined with antibody-based protein profiling, to localize the expression to specific cell types. Altogether, 221 genes were found to be elevated in the lung compared with their expression in other analyzed tissues. Among the gene products were several well-known markers, but also several proteins previously not described in the context of the lung. To link the lung-specific molecular repertoire to human disease, survival associations of pneumocyte-specific genes were assessed by using transcriptomics data from 7 non-small-cell lung cancer (NSCLC) cohorts. Transcript levels of 10 genes (SFTPB, SFTPC, SFTPD, SLC34A2, LAMP3, CACNA2D2, AGER, EMP2, NKX2-1, and NAPSA) were significantly associated with survival in the adenocarcinoma subgroup, thus qualifying as promising biomarker candidates. In summary, based on an integrated omics approach, we identified genes with elevated expression in lung and localized corresponding protein expression to different cell types. As biomarker candidates, these proteins may represent intriguing starting points for further exploration in health and disease.
authors.affiliation: Rudbeck Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.affiliation: Science for Life Laboratory, Kungliga Tekniska Högskolan (KTH) Royal Institute of Technology, Stockholm, Sweden;
authors.forename: Linn
authors.initials: L
authors.lastname: Fagerberg
authors.affiliation: Science for Life Laboratory, Kungliga Tekniska Högskolan (KTH) Royal Institute of Technology, Stockholm, Sweden;
authors.forename: Björn
authors.initials: B
authors.lastname: Hallström
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo) and.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Department of Statistics, Dortmund Technical University, Dortmund, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Hellwig
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo) and.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Rudbeck Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Caroline
authors.initials: C
authors.lastname: Kampf
authors.affiliation: Science for Life Laboratory, Kungliga Tekniska Högskolan (KTH) Royal Institute of Technology, Stockholm, Sweden;
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Rudbeck Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; fredrik.ponten@igp.uu.se.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Rudbeck Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
mesh_terms: D000906:Antibodies / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D020543:Proteome; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D000906:Antibodies; D009363:Neoplasm Proteins; D020543:Proteome; D012333:RNA, Messenger
keywords: expression analysis; in situ detection; patients; prognosis