Thomas, BC;
Kay, JD;
Menon, S;
Vowler, SL;
Dawson, SN;
Bucklow, LJ;
Luxton, HJ;
... Whitaker, HC; + view all
(2016)
Whole blood mRNA in prostate cancer reveals a four-gene androgen regulated panel.
Endocrine-related Cancer
, 23
(10)
pp. 797-812.
10.1530/ERC-16-0287.
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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.
| Type: | Article |
|---|---|
| Title: | Whole blood mRNA in prostate cancer reveals a four-gene androgen regulated panel |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1530/ERC-16-0287 |
| Publisher version: | http://dx.doi.org/10.1530/ERC-16-0287 |
| Language: | English |
| Additional information: | © 2016 Society for Endocrinology. This manuscript has been accepted for publication in Endocrine-related Cancer, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at 10.1530/ERC-16-0287 [2016]. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Endocrinology & Metabolism, PAXgene, prostate cancer, androgen receptor, biomarker, CIRCULATING TUMOR-CELLS, PERIPHERAL-BLOOD, SUPEROXIDE-DISMUTASE, FREE DNA, EXPRESSION, GENE, MARKER, MEN, RECEPTOR, ANTIGEN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1515866 |
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