Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups

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Alshaker, Heba, Mills, Robert, Hunter, Ewan, Salter, Matthew, Ramadass, Aroul, Skinner, Benjamin Matthew, Westra, Willem, Green, Jayne, Akoulitchev, Alexandre, Winkler, Mathias and Pchejetski, Dmitri (2021) Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups. Journal of Translational Medicine, 19 (1). ISSN 1479-5876

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Abstract

Background Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with PCa. Predicting the risk of PCa is pivotal for making an informed decision on treatment options as the 5-year survival rate in the low-risk group is more than 95% and most men would benefit from surveillance rather than active treatment. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can serve as a disease biomarker. Methods In this prospective study we screened whole blood of newly diagnosed, treatment naïve PCa patients (n = 140) and cancer-free controls (n = 96) for the presence of 14,241 chromosomal loops in the loci of 425 genes. Results We have detected specific chromosome conformation changes in the loci of ETS1, MAP3K14, SLC22A3 and CASP2 genes in peripheral blood from PCa patients yielding PCa detection with 80% sensitivity and 80% specificity. Further analysis between PCa risk groups yielded prognostic validation sets consisting of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes that achieved 80% sensitivity and 93% specificity stratifying high-risk category 3 vs low risk category 1 and 84% sensitivity and 89% specificity stratifying high risk category 3 vs intermediate risk category 2 disease. Conclusions Our results demonstrate specific chromosome conformations in the blood of PCa patients that allow PCa diagnosis and risk stratification with high sensitivity and specificity.

Item Type:	Article
Uncontrolled Keywords:	blood test,diagnosis,epigenetics,nucleome,prognosis,prostate cancer,biochemistry, genetics and molecular biology(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?... https://translational-medicine.biomedcen...
Depositing User:	LivePure Connector
Date Deposited:	03 Feb 2021 00:59
Last Modified:	22 Oct 2022 08:34
URI:	https://ueaeprints.uea.ac.uk/id/eprint/79148
DOI:	10.1186/s12967-021-02710-y

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