## 4 Discussion  
The current study found four differently expressed miRNAs in the PCOS patients. MiR-320a-5p, miR-103a-5p, miR-15a-5p and miR-194-5p were all up-regulated in the PCOS group compared to the healthy control group, and miR-15a-5p was up-regulated in the PCOS group compared to the HAC group also. Plasma miR-320-5p and miR-103a-5p demonstrated the highest specificity and sensitivity for diagnosing PCOS, followed by miR-15a-5p, and these miRNAs could be used as independent diagnostic markers for PCOS patients. Furthermore, the latter miRNA showed a very good sensitivity profile  
Figure 2: ROC curves of miR-15a-5p utilized to differentiate patients with polycystic ovary syndrome (PCOS) from (**a**) healthy control (HC) and (**b**) hyperandrogenic control (HAC) groups, and ROC curves of (**c**) miR-320-5p, (**d**) miR-103a-5p, and (**e**) miR-194-5p employed to distinguish PCOS patients from HC. in distinguishing PCOS women not only from healthy individuals but also from female patients with other hyperandrogenic conditions. In recent years, extensive research on the diagnostic potential of different miRNAs as biomarkers for PCOS or PCOS-related metabolic disorders has been carried out but mainly in reproductive-age adult women. The number of studies concerning adolescents with PCOS is limited. [PERSON] et al. were the first to conduct a study in adolescents. It included 31 girls with PCOS, without obesity, and 13 controls. MiR-451a, miR-652-3p, miR-106b-5p and miR-206 were significantly down-regulated in PCOS girls compared to controls [13]. The authors found miR-451a to be 100% sensitive and 100% specific, miR-652-3p to be 81% sensitive and 100% specific and miR-106b-5p to be 100% sensitive and 85% specific for diagnosing PCOS. An inverse correlation was found with the degree of androgen excess and HOMA-IR for miR-451a, miR-652-3p, miR-106b-5p and miR-206, and a positive correlation with SHBG levels [13]. In our study, we did not find significant differences in the relative expression levels of miR-451a in the PCOS patients and the controls and could not confirm the described correlations. Though the number and age of the participants in both studies are similar, in our study, most of the participants were overweight/obese (65% of PCOS girls, 59% of healthy controls and 43% of HAC), which probably attributes to the difference in the results. In a study by [PERSON] et al., serum mirR-28-3p, miR-103a-3, miR-139-5p and miR-376a-3p were found to be significantly down-regulated in women with PCOS [18]. MiR-28-3p and miR-139-5p correlated with the total testosterone and LH:SFH ratio. MiR-28-3p expressed a specificity of 100% and a sensitivity of 59%. It has been reported to be associated with granulosa cell proliferation [18]. In the present study, we assessed the relative expression of miR-28-5p, which has been reported to be associated with granulosa cell proliferation, and is found to be dysregulated in ovarian and other types of cancers [25]. We did not find significant differences in the relative expression of miR-28-5p in the patients and the control groups. Mir-320 is involved in glucose and lipid metabolism and is a potential biomarker for associated metabolic disorders [19]. [PERSON] et al. in their study found low serum expression levels of miR-320 in women with PCOS, compared to healthy controls. The expression of miR-320 correlated with fasting glucose, insulin levels and HOMA-IR, independently of age, BMI and androgen levels [26]. [PERSON] et al. found lower serum miR-320 expression levels in PCOS patients compared to controls and negative correlation with fasting serum insulin, HOMA-IR and PCOS phenotype. The sensitivity of serum miR-320 expression levels for the diagnosis of PCOS was 80% and the specificity was 97.5% [27]. On the other hand, [PERSON] et al. did not find significant differences in the expression levels of miR-320 in 50 women with PCOS or 50 BMI- and age-matched healthy controls [28].