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

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