title: Whole blood mRNA in prostate cancer reveals a four-gene androgen regulated panel.
abstract: Due to increased sensitivity, the expression of circulating nucleotides is rapidly gaining popularity in cancer diagnosis. Whole blood mRNA has been used in studies on a number of cancers, most notably two separate studies that used whole blood mRNA to define non-overlapping signatures of prostate cancer that has become castration independent. Prostate cancer is known to rely on androgens for initial growth, and there is increasing evidence on the importance of the androgen axis in advanced disease. Using whole blood mRNA samples from patients with prostate cancer, we have identified the four-gene panel of FAM129A, MME, KRT7 and SOD2 in circulating mRNA that are differentially expressed in a discovery cohort of metastatic samples. Validation of these genes at the mRNA and protein level was undertaken in additional cohorts defined by risk of relapse following surgery and hormone status. All the four genes were downregulated at the mRNA level in the circulation and in primary tissue, but this was not always reflected in tissue protein expression. MME demonstrated significant differences in the hormone cohorts, whereas FAM129A is downregulated at the mRNA level but is raised at the protein level in tumours. Using published ChIP-seq data, we have demonstrated that this may be due to AR binding at the FAM129A and MME loci in multiple cell lines. These data suggest that whole blood mRNA of androgen-regulated genes has the potential to be used for diagnosis and monitoring of prostate cancer.
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Benjamin C
authors: BC
authors: Thomas
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Molecular Diagnostics and Therapeutics GroupUniversity College London, London, UK.
authors: Jonathan D
authors: JD
authors: Kay
authors: Bioinformatics and Statistics Core FacilityCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Astra Zeneca2 Riverside, Granta Park, Cambridge, UK.
authors: Suraj
authors: S
authors: Menon
authors: Bioinformatics and Statistics Core FacilityCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Astra Zeneca2 Riverside, Granta Park, Cambridge, UK.
authors: Sarah L
authors: SL
authors: Vowler
authors: Bioinformatics and Statistics Core FacilityCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Sarah N
authors: SN
authors: Dawson
authors: Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Laura J
authors: LJ
authors: Bucklow
authors: Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Molecular Diagnostics and Therapeutics GroupUniversity College London, London, UK.
authors: Hayley J
authors: HJ
authors: Luxton
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Thomas
authors: T
authors: Johnston
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Molecular and Computational Diagnostics GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Charlie E
authors: CE
authors: Massie
authors: Genomics Core FacilityCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Michelle
authors: M
authors: Pugh
authors: Department of HistopathologyCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Anne Y
authors: AY
authors: Warren
authors: National Institute for Health Research Cambridge Biomedical Research Centre Core Biochemistry Assay LaboratoryCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Peter
authors: P
authors: Barker
authors: National Institute for Health Research Cambridge Biomedical Research Centre Core Biochemistry Assay LaboratoryCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Keith
authors: K
authors: Burling
authors: Computational Biology GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Andy G
authors: AG
authors: Lynch
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Anne
authors: A
authors: George
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Johanna
authors: J
authors: Burge
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Marie
authors: M
authors: Corcoran
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Sara
authors: S
authors: Stearn
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Alastair D
authors: AD
authors: Lamb
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK.
authors: Naomi L
authors: NL
authors: Sharma
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK University College Hospital at Westmoreland StreetLondon, UK.
authors: Greg L
authors: GL
authors: Shaw
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Nuffield Department of Surgical SciencesJohn Radcliffe Hospital, Headington, Oxford, UK.
authors: David E
authors: DE
authors: Neal
authors: Uro-Oncology Research GroupCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Biomarker InitiativeCancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK Molecular Diagnostics and Therapeutics GroupUniversity College London, London, UK Hayley.Whitaker@ucl.ac.uk.
authors: Hayley C
authors: HC
authors: Whitaker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology*; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000728:Androgens; D012333:RNA, Messenger
keywords: PAXgene; androgen receptor; biomarker; prostate cancer