TY - JOUR

T1 - Locus-specific methylation of gstp1, rnf219, and kiaa1539 genes with single molecule resolution in cell-free dna from healthy donors and prostate tumor patients: Application in diagnostics

AU - Bryzgunova, Olga

AU - Bondar, Anna

AU - Ruzankin, Pavel

AU - Laktionov, Petr

AU - Tarasenko, Anton

AU - Kurilshikov, Alexander

AU - Epifanov, Rostislav

AU - Zaripov, Marat

AU - Kabilov, Marsel

AU - Laktionov, Pavel

N1 - Funding Information: Funding: The study of Olga Bryzgunova, Anna Bondar, Alexander Kurilshikov, Marat Zaripov, Marsel Kabilov, and Pavel Laktionov was supported by the Russian state budget project via the ICBFM SB RAS No. 121030200173-6 “Diagnostics and therapy of oncological diseases”. The study of Pavel Ruzankin and Anton Tarasenko was supported by the Mathematical Center in Akademgorodok under agreement No. 075-15-2019-1675 with the Ministry of Science and Higher Education of the Russian Federation. The study of Petr Laktionov was supported by the Russian Fundamental Scientific Research (project FWGZ-2021-0017) and the Russian Foundation for Basic Research (project No. 20-34-70141). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539 (also known as FAM214B)) in the blood plasma cell-free DNA (cfDNA) of 20 patients with prostate cancer (PCa), 18 healthy donors (HDs), and 17 patients with benign prostatic hyperplasia (BPH) was studied via the MiSeq platform. The methylation status of two CpGs within the same loci were used as the diagnostic feature for discriminating the patient groups. Many variables had good diagnostic characteristics, e.g., each of the variables GSTP1.C3.C9, GSTP1.C9, and GSTP1.C9.T17 demonstrated an 80% sensitivity at a 100% specificity for PCa patients vs. the others comparison. The analysis of RNF219 gene loci methylation allowed discriminating BPH patients with absolute sensitivity and specificity. The data on the methylation of the genes GSTP1 and RNF219 allowed discriminating PCa patients, as well as HDs, with absolute sensitivity and specificity. Thus, the data on the locus-specific methylation of cfDNA (with single-molecule resolution) combined with a diagnostic approach considering the simultaneous methylation of several CpGs in one locus enabled the discrimination of HD, BPH, and PCa patients.

AB - The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539 (also known as FAM214B)) in the blood plasma cell-free DNA (cfDNA) of 20 patients with prostate cancer (PCa), 18 healthy donors (HDs), and 17 patients with benign prostatic hyperplasia (BPH) was studied via the MiSeq platform. The methylation status of two CpGs within the same loci were used as the diagnostic feature for discriminating the patient groups. Many variables had good diagnostic characteristics, e.g., each of the variables GSTP1.C3.C9, GSTP1.C9, and GSTP1.C9.T17 demonstrated an 80% sensitivity at a 100% specificity for PCa patients vs. the others comparison. The analysis of RNF219 gene loci methylation allowed discriminating BPH patients with absolute sensitivity and specificity. The data on the methylation of the genes GSTP1 and RNF219 allowed discriminating PCa patients, as well as HDs, with absolute sensitivity and specificity. Thus, the data on the locus-specific methylation of cfDNA (with single-molecule resolution) combined with a diagnostic approach considering the simultaneous methylation of several CpGs in one locus enabled the discrimination of HD, BPH, and PCa patients.

KW - Benign prostatic hyperplasia

KW - Cell-free DNA

KW - Locus-specific NGS sequencing

KW - Methylation

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85120990310&partnerID=8YFLogxK

U2 - 10.3390/cancers13246234

DO - 10.3390/cancers13246234

M3 - Article

C2 - 34944854

AN - SCOPUS:85120990310

VL - 13

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 24

M1 - 6234

ER -