Masood Abu-Halima1, Mohamad Hammadeh2, Christina Backes3, Ulrike Fischer3, Petra Leidinger3, Abdel Monem Lubbad4, Andreas Keller3, Eckart Meese3. 1. Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany; Department of Obstetrics and Gynecology, IVF and Andrology Laboratory, Saarland University, Saar, Germany. Electronic address: masood@daad-alumni.de. 2. Department of Obstetrics and Gynecology, IVF and Andrology Laboratory, Saarland University, Saar, Germany. 3. Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany. 4. Faculty of Medicine, Islamic University of Gaza, Gaza Strip, Palestine.
Abstract
OBJECTIVE: To validate a set of five microRNAs (miRNAs) as specific biomarkers for the assessment of male infertility. DESIGN: Quantitative real-time polymerase chain reaction (qRT-PCR) validation study. SETTING: University research and clinical institutes. PATIENT(S): Two hundred twenty-six men presenting at an infertility clinic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Validation analysis of a set of miRNAs in human purified spermatozoa and testicular biopsies. RESULT(S): Five miRNAs (hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p, hsa-miR-429, and hsa-miR-122) were confirmed with the use of qRT-PCR analysis in validation sets in patients with different forms of spermatogenic impairments (subfertile and nonobstructive azoospermia [NOA]) and control subjects. We found that hsa-miR-429 was significantly increased and the four other miRNAs were decreased in both tested groups compared with normal control subjects. Computing the area under the receiver operating characteristic curve (AUC) value for each of the five miRNAs, we showed that they separated the tested groups with high accuracy (range 0.777-0.988), except for hsa-miR-429 (AUC 0.475), in patient samples with NOA. Furthermore, with the use of support vector machine classification combining these five miRNAs, we found that they discriminated individuals with, respectively, subfertility and NOA from control subjects with an accuracy of 98.65% and 99.91%, a specificity of 98.44% and 99.69%, and a sensitivity of 98.83% and 100%. CONCLUSION(S): Our finding suggests that these five miRNAs have potential as novel noninvasive biomarkers to diagnose patients with subfertility. Except for hsa-miR-429, the combination of these miRNAs with other conventional tests would improve the diagnostic accuracy for detecting patients with different forms of NOA.
OBJECTIVE: To validate a set of five microRNAs (miRNAs) as specific biomarkers for the assessment of male infertility. DESIGN: Quantitative real-time polymerase chain reaction (qRT-PCR) validation study. SETTING: University research and clinical institutes. PATIENT(S): Two hundred twenty-six men presenting at an infertility clinic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Validation analysis of a set of miRNAs in human purified spermatozoa and testicular biopsies. RESULT(S): Five miRNAs (hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p, hsa-miR-429, and hsa-miR-122) were confirmed with the use of qRT-PCR analysis in validation sets in patients with different forms of spermatogenic impairments (subfertile and nonobstructive azoospermia [NOA]) and control subjects. We found that hsa-miR-429 was significantly increased and the four other miRNAs were decreased in both tested groups compared with normal control subjects. Computing the area under the receiver operating characteristic curve (AUC) value for each of the five miRNAs, we showed that they separated the tested groups with high accuracy (range 0.777-0.988), except for hsa-miR-429 (AUC 0.475), in patient samples with NOA. Furthermore, with the use of support vector machine classification combining these five miRNAs, we found that they discriminated individuals with, respectively, subfertility and NOA from control subjects with an accuracy of 98.65% and 99.91%, a specificity of 98.44% and 99.69%, and a sensitivity of 98.83% and 100%. CONCLUSION(S): Our finding suggests that these five miRNAs have potential as novel noninvasive biomarkers to diagnose patients with subfertility. Except for hsa-miR-429, the combination of these miRNAs with other conventional tests would improve the diagnostic accuracy for detecting patients with different forms of NOA.
Authors: Julia Alles; Tobias Fehlmann; Ulrike Fischer; Christina Backes; Valentina Galata; Marie Minet; Martin Hart; Masood Abu-Halima; Friedrich A Grässer; Hans-Peter Lenhof; Andreas Keller; Eckart Meese Journal: Nucleic Acids Res Date: 2019-04-23 Impact factor: 16.971
Authors: Filipe Tenorio Lira Neto; Phil Vu Bach; Bobby Baback Najari; Philip Shihua Li; Marc Goldstein Journal: Curr Urol Rep Date: 2016-10 Impact factor: 3.092