Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

Gillian O'Hurley; Christer Busch; Linn Fagerberg; Björn M Hallström; Charlotte Stadler; Anna Tolf; Emma Lundberg; Jochen M Schwenk; Karin Jirström; Anders Bjartell; William M Gallagher; Mathias Uhlén; Fredrik Pontén

doi:10.1371/journal.pone.0133449

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PLoS One. 2015 Aug 3;10(8):e0133449. doi: 10.1371/journal.pone.0133449. eCollection 2015.

Affiliations

¹ Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; OncoMark Ltd, NovaUCD, Belfield Innovation Park, Belfield, Dublin 4, Ireland.
² Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
³ Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
⁴ Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
⁵ Department of Clinical Sciences, Division of Urological Cancers, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
⁶ UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Abstract

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acyl-CoA Oxidase / analysis
Acyl-CoA Oxidase / genetics*
Aged
Animals
Antibodies / analysis
Biomarkers, Tumor / analysis
Biomarkers, Tumor / genetics
Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Gene Regulatory Networks
Humans
Immunohistochemistry
Male
Membrane Proteins / analysis
Membrane Proteins / genetics*
Middle Aged
Prostate / metabolism
Prostate / pathology*
Prostatic Neoplasms / diagnosis*
Prostatic Neoplasms / genetics*
Proteome / genetics
Proteomics
RNA, Messenger / genetics
Rabbits
Sequence Analysis, RNA
Transcriptome

Substances

Antibodies
Biomarkers, Tumor
Membrane Proteins
Proteome
RNA, Messenger
Tmem79 protein, human
ACOXL protein, human
Acyl-CoA Oxidase

Grants and funding

Funding was provided by the Knut and Alice Wallenberg Foundation and the Swedish Cancer Foundation and by the Marie Curie Industry-Academia Partnerships and Pathways program, FAST-PATH (No. 285910). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. OncoMark Ltd provided support in the form of salaries for author GOH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.