TY - JOUR

T1 - Searching for the novel specific predictors of prostate cancer in urine

T2 - The analysis of 84 miRNA expression

AU - Lekchnov, Evgeniy A.

AU - Amelina, Evgeniya V.

AU - Bryzgunova, Olga E.

AU - Zaporozhchenko, Ivan A.

AU - Konoshenko, Mariya Yu

AU - Yarmoschuk, Sergey V.

AU - Murashov, Ivan S.

AU - Pashkovskaya, Oxana A.

AU - Gorizkii, Anton M.

AU - Zheravin, Aleksandr A.

AU - Laktionov, Pavel P.

PY - 2018/12/17

Y1 - 2018/12/17

N2 - The aim of this study was to investigate miRNA profiles of clarified urine supernatant and combined urine vesicle fractions of healthy donors and patients with benign prostatic hyperplasia and prostate cancer (PCa). The comparative analysis of miRNA expression was conducted with a custom miRCURY LNA miRNA qPCR panel. Significant combinations of miRNA pairs were selected by the RandomForest-based feature selection algorithm Boruta; the difference of the medians between the groups and a 95% confidence interval was built using the bootstrap approach. The Asymptotic Wilcoxon-Mann-Whitney Test was performed for miRNA combinations to compare different groups of donors. Benjamini-Hochberg correction was used to adjust the statistical significance for multiple comparisons. The most diagnostically significant miRNAs pairs were miR-107-miR-26b.5p and miR-375.3p-miR-26b.5p in the urine supernatant fraction that discriminated the group of healthy patients and PCa patients, as well as miR-31.5p-miR-16.5p, miR-31.5p-miR-200b, miR-31.5p-miR-30e.3p and miR-31.5p-miR-660.5p in the fraction extracellular vesicles that were different between healthy men and benign prostate hyperplasia patients. Such statistical criteria as the occurrence of individual significant miRNA pairs in the total number of comparisons, median ∆C t difference, and confidence interval can be useful tools for determining reliable markers of PCa.

AB - The aim of this study was to investigate miRNA profiles of clarified urine supernatant and combined urine vesicle fractions of healthy donors and patients with benign prostatic hyperplasia and prostate cancer (PCa). The comparative analysis of miRNA expression was conducted with a custom miRCURY LNA miRNA qPCR panel. Significant combinations of miRNA pairs were selected by the RandomForest-based feature selection algorithm Boruta; the difference of the medians between the groups and a 95% confidence interval was built using the bootstrap approach. The Asymptotic Wilcoxon-Mann-Whitney Test was performed for miRNA combinations to compare different groups of donors. Benjamini-Hochberg correction was used to adjust the statistical significance for multiple comparisons. The most diagnostically significant miRNAs pairs were miR-107-miR-26b.5p and miR-375.3p-miR-26b.5p in the urine supernatant fraction that discriminated the group of healthy patients and PCa patients, as well as miR-31.5p-miR-16.5p, miR-31.5p-miR-200b, miR-31.5p-miR-30e.3p and miR-31.5p-miR-660.5p in the fraction extracellular vesicles that were different between healthy men and benign prostate hyperplasia patients. Such statistical criteria as the occurrence of individual significant miRNA pairs in the total number of comparisons, median ∆C t difference, and confidence interval can be useful tools for determining reliable markers of PCa.

KW - Extracellular vesicles

KW - MiRNA

KW - Prostate cancer

KW - Urine

KW - Humans

KW - Middle Aged

KW - RNA, Neoplasm/urine

KW - Gene Expression Regulation, Neoplastic

KW - Male

KW - Prostatic Neoplasms/urine

KW - Aged, 80 and over

KW - Aged

KW - MicroRNAs/urine

KW - extracellular vesicles

KW - urine

KW - MARKERS

KW - HYPERPLASIA

KW - BIOMARKERS

KW - prostate cancer

KW - miRNA

KW - ANTIGEN

KW - MICRORNA

UR - http://www.scopus.com/inward/record.url?scp=85058900998&partnerID=8YFLogxK

U2 - 10.3390/ijms19124088

DO - 10.3390/ijms19124088

M3 - Article

C2 - 30562989

AN - SCOPUS:85058900998

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 12

M1 - 4088

ER -