Serum miR-141-3p serves as a biomarker for early-stage diagnosis of endometriosis

The clinical data of patients in the endometriosis ( n  = 246) and control groups ( n  = 87) were analyzed. As shown in Table  1 , endometriosis patients exhibited remarkably higher levels of abortion history, uterine operation history, endometriosis family history, endometriosis history, duration of dysmenorrhea, FSH, and CA125 level, but markedly lower AMH than control people (all p  < 0.05). Table 1 Baseline data of patients Endometriosis( n  = 246) Control( n  = 87) z/t/x 2 P Age (years) 32(21, 52) 31(21, 51) 0.756 0.450 BMI(kg/m 2 ) 20.95(15.81, 29.09) (19.03, 24.49) 0.522 0.602 MAP(mmHg) 94.28 ± 1.44 94.06 ± 1.62 1.205 0.229 Smoking history 1.358 0.244 Yes 54(21.95) 14(16.09) No 192(78.05) 73(83.91) Alcohol history 0.136 0.712 Yes 73(26.68) 24(27.59) No 173(70.32) 63(72.41) Abortion history 7.515 0.006 Yes 121(49.18) 28(32.18) No 125(50.81) 59(67.82) Operation history of uterine cavity 6.861 0.009 Yes 101(41.06) 22(25.29) No 145(58.94) 65(74.71) Endometriosis family history 8.313 0.004 Yes 46(18.70) 5(5.75) No 200(81.31) 82(94.25) Endometriosis history 18.636 < 0.001 Yes 65(26.42) 4(4.60) No 181(73.58) 83(95.40) Duration of dysmenorrhea (years) 5(1, 10) 2(0, 7) 10.613 < 0.001 E2(pmol/L) 142.98 ± 23.63 144.87 ± 26.06 0.624 0.533 LH(IU/L) 4.73 ± 1.25 4.71 ± 1.46 0.077 0.943 FSH(IU/L) 3.56 ± 0.40 1.98 ± 0.61 22.539 < 0.001 AMH(ng/mL) 2.15 ± 0.12 3.35 ± 0.57 19.464 < 0.001 CA125 (U/mL) 44.62 ± 8.49 24.78 ± 4.33 27.837 < 0.001 Note: BMI  body mass Index, MAP  mean aortic pressure, E2 estrogen, LH  luteinizing hormone, FSH  follicle-stimulating hormone, AMH  anti-Müllerian hormone; CA125, Cancer Antigen 125. The Kolmogorov-Smirnov test was employed for the normal distribution test. The measurement data with normal distribution were represented as mean ± standard deviation and the independent sample t -test was utilized for inter-group comparison. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and the Mann-Whitney U test was used for inter-group comparisons. The count data between groups were expressed as cases (percentage) and analyzed utilizing the Chi-square test or Fisher’s exact test Baseline data of patients Note: BMI  body mass Index, MAP  mean aortic pressure, E2 estrogen, LH  luteinizing hormone, FSH  follicle-stimulating hormone, AMH  anti-Müllerian hormone; CA125, Cancer Antigen 125. The Kolmogorov-Smirnov test was employed for the normal distribution test. The measurement data with normal distribution were represented as mean ± standard deviation and the independent sample t -test was utilized for inter-group comparison. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and the Mann-Whitney U test was used for inter-group comparisons. The count data between groups were expressed as cases (percentage) and analyzed utilizing the Chi-square test or Fisher’s exact test Research has shown that miR-141-3p expression is remarkably reduced in EM tissues [ 18 – 20 ]. Serum miR-141-3p expression was further detected using RT-qPCR, and it was found that serum miR-141-3p expression in the endometriosis group [0.37 (0.07, 1.32)] was remarkably lower than that in the control group [1.11 (0.27, 1.89)] ( p < 0.001) (Fig. 1 A). Based on these findings, miR-141-3p was downregulated in endometriosis, and miR-141-3p downregulation may be a potential biomarker for endometriosis occurrence. Subsequently, the diagnostic value of serum miR-141-3p expression for endometriosis occurrence was clarified. According to ROC analysis results, serum miR-141-3p [area under the curve (AUC) = 0.916, 95CI% = 0.881–0.944, p < 0.001, sensitivity = 94.72%, specificity = 74.71%, cutoff value = 0.89] had high diagnostic value for endometriosis patients (Fig. 1 B). Fig. 1 miR-141-3p expression had a high auxiliary diagnostic value for endometriosis patients. A  Serum miR-141-3p expression in the endometriosis group and control group was tested. The Kolmogorov-Smirnov test was employed for the normal distribution test. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and Mann-Whitney U test was used for inter-group comparisons.*** p  < 0.001; B  the diagnostic value of serum miR-141-3p expression for endometriosis occurrence was clarified through ROC analysis miR-141-3p expression had a high auxiliary diagnostic value for endometriosis patients. A  Serum miR-141-3p expression in the endometriosis group and control group was tested. The Kolmogorov-Smirnov test was employed for the normal distribution test. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and Mann-Whitney U test was used for inter-group comparisons.*** p  < 0.001; B  the diagnostic value of serum miR-141-3p expression for endometriosis occurrence was clarified through ROC analysis According to the cutoff value of miR-141-3p for diagnosing endometriosis patients (0.89), endometriosis patients were allocated into the H-miR-141-3p group (> 0.89, n  = 14) and L-miR-141-3p group (≤ 0.89, n  = 232). The relationship between different serum miR-141-3p expressions and endometriosis patients’ clinical pathological characteristics (pathological classification, cyst location, endometrial cycle, ectopic cyst size, clinical r-AFS staging) was analyzed. Among patients with endometriosis, the proportion of Stage III-IV cases was significantly higher in the L-miR-141-3p group compared to the H-miR-141-3p group (all p  < 0.05) (Table  2 ), suggesting that serum miR-141-3p expression is closely associated with clinical r-AFS staging in endometriosis patients. These findings indicated a close correlation between serum miR-141-3p expression and ectopic cyst size and clinical r-AFS staging in endometriosis patients. Table 2 Endometriosis patients’ clinical pathological characteristics H-miR-141-3p ( n  = 14) L-miR-141-3p ( n  = 232) P Pathological classification (mean, %) 0.157 Ovarian endometriosis 10 (71.43) 146 (62.93) Peritoneal endometriosis 3 (21.43) 83 (35.78) Deep infiltrating endometriosis 1 (7.14) 3 (1.29) Cyst location (case, %) 0.697 Unilateral 10 (71.43) 154 (66.38) Bilateral 4 (25.57) 78 (33.62) Endometrial cycle (case, %) 0.386 Proliferative phase 7 (50.00) 143 (61.64) Secretory phase 7 (50.00) 89 (38.36) Ectopic cyst size (case, %) 0.058 < 4 cm 11 (78.57) 122 (52.59) ≥ 4 cm 3 (21.43) 110 (47.41) r-AFS staging (case, %) < 0.001 I-II stage 3 (21.43) 155 (66.81) III-IV stage 11 (78.57) 77 (33.19) Note: r-AFS, revised American Fertility Society. The count data between groups were expressed as cases (percentage) and analyzed utilizing the Chi-square test or Fisher’s exact test Endometriosis patients’ clinical pathological characteristics Note: r-AFS, revised American Fertility Society. The count data between groups were expressed as cases (percentage) and analyzed utilizing the Chi-square test or Fisher’s exact test As mentioned earlier [ 15 ], patients with endometriosis were allocated into the early-endometriosis (stage I-II, n = 88) and severe-endometriosis (III-IV, n = 158) groups. Comparison of serum miR-141-3p expression between these two groups revealed that serum miR-141-3p expression in the severe-endometriosis group was notably lower than that in the early-endometriosis group ( p < 0.001) (Fig. 2 A). Subsequently, the correlation of serum miR-141-3p expression with EHP-30 score was analyzed using Spearman, and the results revealed a significant correlation ( r = −0.755, 95% CI = −0.805 to −0.693) ( p < 0.001) (Fig. 2 B). These findings indicated serum miR-141-3p expression in endometriosis patients decreased as the disease severity worsened. Fig. 2 Serum miR-141-3p expression in endometriosis patients was negatively correlated with disease severity. A  Serum miR-141-3p expression in the early-endometriosis ( n  = 88) and severe-endometriosis ( n  = 158) groups was analyzed. The Kolmogorov-Smirnov test was employed for normal distribution test. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and Mann-Whitney U test was used for inter-group comparisons. *** p  < 0.001; B  the relationship between serum miR-141-3p expression and EHP-30 score in endometriosis patients was analyzed using Spearman, r was the correlation coefficient Serum miR-141-3p expression in endometriosis patients was negatively correlated with disease severity. A  Serum miR-141-3p expression in the early-endometriosis ( n  = 88) and severe-endometriosis ( n  = 158) groups was analyzed. The Kolmogorov-Smirnov test was employed for normal distribution test. The non-normally distributed measurement data were represented as median (minimum, maximum) values, and Mann-Whitney U test was used for inter-group comparisons. *** p  < 0.001; B  the relationship between serum miR-141-3p expression and EHP-30 score in endometriosis patients was analyzed using Spearman, r was the correlation coefficient Serum miR-141-3p expression in patients in the early-endometriosis group and control group was analyzed. As indicated by the results, patients in the early-endometriosis group showed remarkably lower serum miR-141-3p expression relative to the controls ( p  < 0.001) (Fig.  3 A). The auxiliary diagnostic significance of serum miR-141-3p in early-stage endometriosis patients was further investigated. According to ROC analysis results, serum miR-141-3p (AUC = 0.858, 95CI% = 0.797–0.906, p  < 0.001, sensitivity = 87.50%, specificity = 74.71%, cutoff value = 0.88) can assist in the diagnosis of early-stage endometriosis patients (Fig.  3 B). We further investigated whether combining serum miR-141-3p with the established biomarker CA125 could enhance diagnostic performance. The results showed that the combination of serum miR-141-3p and CA125 significantly improved diagnostic accuracy for early-stage endometriosis (AUC = 0.958, 95% CI = 0.933–0.983, p  < 0.001; sensitivity = 89.77%, specificity = 89.66%, cutoff value = 0.45), compared to either marker alone—miR-141-3p or CA125 (AUC = 0.879, 95% CI = 0.831–0.927, p  < 0.001; sensitivity = 64.77%, specificity = 94.25%, cutoff value = 34.80) (all p  < 0.0001). These findings suggest that combining serum miR-141-3p with CA125 can further enhance diagnostic performance for early-stage endometriosis. Fig. 3 early-stage endometriosis early-stage endometriosis

A total of 284 patients with endometriosis who underwent laparoscopic examination in the Hunan Provincial Maternal and Child Health Care Hospital (October 2020-October 2022) were retrospectively included. Patients were enrolled following the criteria as follows: (1) age > 20 years; (2) complete clinical data; and (3) meeting the indications for laparoscopic examination. The exclusion criteria were: (1) female reproductive tract abnormalities; (2) immune system-related diseases; (3) surgery history for other ovarian lesions; (4) administration history of hormone contraceptives, leuprorelin, and other medications over the past six months; (5) adenomyosis, endometrial polyps, other endometrial diseases or uterine fibroids and pelvic inflammatory disease; (6) complications with serious diseases such as malignant tumors, thyroid diseases, autoimmune diseases, severe cardiovascular diseases, and liver and kidney dysfunction; (7) history of nonsteroidal anti-inflammatory drug treatment or anesthesia analgesia over the past six months; (8) history of pregnancy or breastfeeding over the past six months; (9) mental disorders and inability to complete scale tests. After screening, 246 patients with endometriosis were ultimately included as the study subjects. During the same period, 103 healthy women with normal indicators were enrolled according to the following criteria: (1) age > 20 years; (2) complete data; (3) normal indexes; (4) normal clinical indicators: normal gynecological examination [no palpable pelvic mass on bimanual examination, no fixed uterine tenderness (to exclude deep infiltrating endometriosis)]; normal imaging evaluation (transvaginal ultrasound excludes ovarian endometrioma, adenomyosis, pelvic inflammatory disease, uterine fibroids, endometrial polyps, and chronic endometritis); normal cervical cytology (to exclude cervical cancer); CA125 < 35 U/mL (to exclude occult lesions); and regular menstruation. The exclusion threshold were: (1) surgical treatment over the past six months; (2) breastfeeding or pregnant women; (3) history of treatment with hormone contraceptives and other medications over the past six months. After screening, 87 healthy women were finally included as the control group. This study followed the ethical guidelines of the Helsinki Declaration and relevant norms and regulations for clinical research and complied with the Enhancing the Quality and Transparency of Health Research (EQUATOR) network guidelines. This study got approval from the Academic Ethics Committee of the Hunan Provincial Maternal and Child Health Care Hospital. Typical symptoms include severe dysmenorrhea, deep sexual pain, chronic pelvic pain, infertility, dysuria (periodic) with or without hematuria, dyschezia (periodic) with or without bloody stools, cyclical dyspnea, chest or shoulder pain, hemoptysis, and pneumothorax [ 12 ]. Additionally, endometriosis patients are characterized by tender nodules in the posterior vaginal fornix, adnexal masses, and uniform enlargement of the uterus, with typical or atypical endometriosis lesions in the pathological examination [ 13 ]. According to the r-AFS classification mentioned earlier [ 14 , 15 ], endometriosis patients were allocated into early-endometriosis (no significant adhesion) and severe-endometriosis (significant adhesion). Early-endometriosis included stage I (solitary lesions) and stage II (superficial lesions with a total diameter < 5 cm). Severe-endometriosis included stage III (multiple superficial and deep lesions) and stage IV (multiple deep lesions and large chocolate cysts). The baseline data of all participants were recorded: age, body mass index (BMI), mean arterial pressure (MAP), smoking history, alcohol history, abortion history, operation history of uterine cavity, endometriosis family history, endometriosis history, duration of dysmenorrhea, clinical indicators [estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), CA125], clinical pathological characteristics (pathological classification, cyst location, endometrial cycle, ectopic cyst size, clinical r-AFS staging), and Endometriosis Health Profile-30 (EHP-30) score. Peripheral circulating blood was collected from all participants during days 5–10 of the menstrual cycle. Samples were processed according to a standardized operating procedure (SOP), with serum collected for reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection. As previously reported [ 16 ], the EHP-30 score was employed to assess the health status of endometriosis patients. The EHP-30 scale includes five dimensions (pain, control and helplessness, emotional well-being, social support, and self-image) and can comprehensively and accurately reflect physical and mental health status of endometriosis patients. The total score of the EHP-30 scale is 100, with higher scores indicating poorer health status of endometriosis patients. This scale had a Cronbach’s α coefficient of 0.736 to 0.976, indicating its high reliability and validity, and it can stably reflect the health status of endometriosis patients. As previously mentioned [ 17 ], serum total RNA was extracted using TRIzol regent (Invitrogen Inc., Carlsbad, CA, USA) and reverse transcribed into cDNA using TaqMan™ MicroRNA reverse transcription kit (4366597, Thermo Fisher Scientific Co., Ltd., IL, USA). The SYBR Green qPCR SuperMix (Solarbio, Beijing, China) was used for RT-qPCR in the ABI PRISM 7900 PCR system (Applied Biosystem, ForsterCity, CA, USA). The reaction conditions were: 10-min pre-denaturation at 95 °C, 10-s denaturation at 95 °C, 20-s annealing at 60 °C, and 34-s extension at 72 °C, for a total of 40 cycles. All data were repeated three times in the experiment. The amplification efficiency and specificity of the primers were confirmed through amplification curves and melting curves, and the target gene relative expression was calculated. With cel-miR-39 as an exogenous reference, the relative expression of miR-141-3p in serum was detected through RT-qPCR, and the results were analyzed utilizing the 2 −ΔΔCT method. Primer sequences are listed in Supplementary Table 1. No significant difference in cel-miR-39 expression was observed between the two groups ( p >0.05), as shown in Supplementary Fig. 1. Sample size estimation was performed using G*Power 3.1.9.2 software developed by the University of Düsseldorf. The parameters were set as follows: power = 0.95, α = 0.05, and effect size = 0.5. The results indicated that a minimum of 201 endometriosis patients and 71 control subjects were required, with a total minimum sample size of N  = 272. Considering an estimated dropout rate of approximately 10%, a total of 246 endometriosis patients and 87 control subjects were ultimately enrolled in the study (Supplementary Fig. 2). SPSS (21.0, SPSS, Inc, Chicago, IL, USA) and GraphPad Prism (8.0.1, GraphPad Software Inc., San Diego, CA, USA) were employed for data statistical analysis and plotting. The Kolmogorov-Smirnov test was utilized for the normal distribution test. The normally and non-normally distributed measurement data were shown as mean ± standard deviation and median (minimum, maximum) values, separately, and analyzed for inter-group comparison through the independent sample t -test and Mann-Whitney U test, respectively. The count data were shown in the form of cases (percentage), with inter-group difference compared using the Chi-square or Fisher’s exact test. Receiver operating characteristic (ROC) analysis was performed using SPSS version 21.0 to evaluate the diagnostic value of serum miR-141-3p for endometriosis and early-stage endometriosis. The optimal cutoff value was determined based on the maximum Youden’s index. The association of serum miR-141-3p expression with EHP-30 score in endometriosis patients was analyzed through Spearman, with r as the correlation coefficient. The test level α = 0.05, P is a two-sided test, with p  < 0.05 indicating a statistical significance of the difference.

Endometriosis notably affects the daily physical and psychosocial function of patients [ 21 ]. miRNAs are tightly implicated in the progression of endometriosis [ 18 ]. Most scholars have confirmed through cell experiments in the basic research that miR-141-3p regulates endometriosis cell proliferation, migration and invasion and can reverse epithelial-mesenchymal transition (EMT) [ 18 – 20 ]. However, few studies have analyzed the correlation between miR-141-3p and clinicopathological characteristics of endometriosis. This study demonstrated that serum miR-141-3p levels were significantly downregulated in endometriosis patients and showed a negative correlation with disease severity. Additionally, the combined biomarker panel of miR-141-3p and CA125 could further enhance the diagnostic efficacy for the early-stage endometriosis. This synergistic approach provides a clinically actionable strategy for early intervention and potentially enabling timely therapeutic interventions that may alter disease progression trajectories. First, the baseline data characteristics of endometriosis patients and normal people were compared and analyzed. It has been revealed that endometriosis is primarily characterized by symptoms including chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility [ 22 ]. Endometriosis patients show a notable decrease in AMH and an elevation in serum FSH levels as compared to normal controls [ 23 ]. Subsequently, the mechanism of endometriosis pathogenesis was further investigated. It has been widely accepted that miRNAs play crucial roles in modulating multiple biological pathways and processes, exerting notable physiological effects [ 24 ]. Accumulating studies have provided evidence for the tight implication of miR-141-3p in various disorders. For example, miR-141-3p was remarkably poorly expressed in clear cell renal cell carcinoma cells, and miR-141-3p overexpression could inhibit cancer cell growth and facilitate apoptosis [ 25 ]. miR-141-3p is downregulated in acute respiratory distress syndrome patients, showing great potential in its diagnosis [ 17 ]. In this study, downregulated miR-141-3p was observed in serum of endometriosis patients, and downregulated serum miR-141-3p expression may be a biomarker for endometriosis occurrence. Similarly, a previous study has also demonstrated a poor expression of miR-141-3p in endometriosis, highlighting miR-141-3p as a new marker for endometriosis treatment [ 18 ]. According to the miRCURY™ LNA microarray screening results, the expression level of miR-141-3p in menstrual blood is 27.95 times higher than that in peripheral blood [ 26 ]. Whether measuring miR-141-3p levels in menstrual blood could improve its diagnostic performance warrants further investigation. However, studies have shown that miR-141-3p expression may fluctuate during the follicular phase [ 27 , 28 ]. Unfortunately, our study did not control for menstrual cycle-related variability, which should be addressed in future investigations. Next, endometriosis patients in the H-miR-141-3p group had a higher proportion of ectopic cyst sizes ≥ 4 cm and stages III-IV relative to those in the L-miR-141-3p group. This negative association with r-AFS staging supports its potential utility in clinical classification. In support of these findings, it has been shown that endometriosis presents with ectopic endometriotic lesions [ 29 ]. miR-141-3p may contribute to endometriosis progression [ 19 ]. Most studies have shown that miR-141-3p can inhibit NLRP3-mediated pyroptosis in endometriosis, and overexpression of NLRP3 reverses the protective effect of miR-141-3p overexpression on renal tubular epithelial cells [ 10 , 30 ]. However, there are few reports on the clinical application of miR-141-3p in endometriosis, which further demonstrates the novelty of this study. Moreover, this study revealed that serum miR-141-3p expression in endometriosis patients was negatively correlated with disease severity. As has been evidenced previously, the EHP-30 is commonly used to evaluate the effects of endometriosis on the life quality of patients, measuring different aspects of endometriosis-associated health [ 31 ]. miR-141-3p expression is gradually reduced from normal endometria to eutopic endometria, then to ectopic endometria tissues [ 20 ]. Mechanistically, miR-141-3p, as a key member of the miR-200 family, plays a critical role in the pathogenesis of endometriosis. Several factors may explain its downregulation in endometriosis: (1) miR-141-3p is a potent suppressor of epithelial-mesenchymal transition (EMT), and its reduced expression facilitates the migration and invasion of endometrial cells, promoting ectopic lesion formation [ 32 – 34 ]; (2) overexpression of miR-141-3p can suppress pro-inflammatory cytokines, whereas its downregulation may exacerbate inflammation, fostering a microenvironment supportive of ectopic endometrial survival [ 35 ]; (3) miR-141-3p has been shown to target KLF-12 to inhibit proliferation and migration while promoting apoptosis of ectopic endometrial stromal cells; its reduced expression leads to decreased apoptosis and enhanced lesion survival [ 18 ]. Furthermore, hormonal regulation may also contribute to its dysregulation, as miR-141-3p is affected by estrogen and progesterone through ER/PR signaling pathways [ 36 , 37 ]. To further improve diagnostic accuracy, we evaluated the combined use of miR-141-3p and CA125, which yielded significantly enhanced performance. This combination may be particularly valuable for early-stage diagnosis. Despite these promising results, several critical challenges must be addressed before serum miR-141-3p can be translated into clinical practice: (1) Standardization: In this study, we minimized variability by processing blood samples using a unified SOP; (2) Cost-effectiveness: Current diagnostic approaches like laparoscopy are invasive and costly, while ultrasound has limited sensitivity. miR-141-3p testing costs approximately one-tenth of laparoscopy. Given the specificity of 74.71%, clinicians must weigh the risk of false positives, although miR-141-3p testing may be suitable for preliminary screening in high-risk populations (such as patients with dysmenorrhea, infertility, or family history); (3) Technical variability: Despite using U6 as an internal control and performing triplicates, differences in primer design (such as stem-loop vs. polyA tailing) or amplification systems may influence reproducibility. Future multi-center validation is needed. It is also worth noting that this study did not include differential diagnostic analyses against related conditions such as adenomyosis, pelvic inflammatory disease, or ovarian cysts, which limits the current applicability of our findings. Further studies are warranted to assess whether serum miR-141-3p has sufficient discriminatory power in differentiating endometriosis from other gynecological conditions. Once validated, serum miR-141-3p could be used for screening high-risk populations—such as asymptomatic individuals with a family history, or patients with endometriosis-related symptoms but negative ultrasound findings. In individuals with significantly reduced miR-141-3p and elevated CA125, further laparoscopic confirmation should be recommended. Beyond the aforementioned challenges related to clinical translation, this study also has several additional limitations. First, this study is retrospective, and the sample size may affect the reliability of the results. Second, this study only included individuals of East Asian descent, limiting generalizability across racial groups. Future prospective, multi-ethnic, and multi-center studies are essential. Additionally, given the complex molecular regulatory networks of miRNAs, further research is required to identify target genes and signaling pathways involved in miR-141-3p-mediated pathogenesis. In summary, this article demonstrated miR-141-3p downregulation in endometriosis. Additionally, we innovatively explored its clinical performance in endometriosis. We also explored its clinical relevance and proposed its use as a potential early-stage diagnostic biomarker.

Endometriosis is a typically chronic and gynecological disease, influencing 5–10% of reproductive-aged women across the world [ 1 ]. Endometriosis is pathologically characterized by the existence of endometrial tissues outside the uterus, accompanied by pelvic pain and infertility [ 2 ]. Pregnant women with endometriosis are more likely to be prone to adverse outcomes, highlighting the urgency for more and more clinical awareness of endometriosis [ 3 ]. It is of great value to prevent endometriosis at its early stage to effectively manage endometriosis progression; endometriosis is best detected during adolescence [ 4 ]. However, currently, in addition to surgery and scans, there is no other available approach for early-stage diagnosis and treatment of endometriosis; unless a series of symptoms (such asinfertility and pain) occur, identifying endometriosis at the onset is difficult [ 5 ]. Hence, it’s of great urgency to explore new markers for preventing and treating endometriosis in its early stage. microRNAs (miRNAs), a series of endogenous RNAs, can modulate gene expression, and changes in miRNA expression may lead to alterations in genes associated with extensive biological processes and even facilitate the occurrence of various human disorders [ 6 ]. Previous research demonstrated altered expression levels of various miRNAs in endometriotic lesions and eutopic endometrium of endometriosis patients, highlighting an undeniable association between miRNAs and the pathology of endometriosis [ 7 ]. miR-141-3p, a specific miRNA, has been evidenced to be tightly implicated in various diseases. For example, miR-141-3p can protect against blood-brain barrier disruption and alleviate intracerebral hemorrhage-induced brain injuries [ 8 ]. miR-141-3p is poorly expressed in polycystic ovary syndrome patients, showing not only high diagnostic performance for polycystic ovary syndrome but a close link to glucose and lipid metabolism [ 9 ]. Furthermore, it has been shown that miR-141-3p may act as a sponge of lncRNA MALAT1, thus exerting effects on NLRP3-induced pyroptosis and fibrosis in endometriosis [ 10 ]. Additionally, miR-141-3p has also been shown to be tightly associated with the development of endometriosis through interactions with lncRNA NEAT1 and HTRA1 [ 11 ]. However, at present, the clinical application of miR-141-3p in patients with endometriosis is not clear. Hence, this study explored the clinical value of miR-141-3p in the early-stage diagnosis of endometriosis. The present study evaluated miR-141-3p expression in the serum of endometriosis patients and assessed the diagnostic value of serum miR-141-3p expression for endometriosis and early endometriosis patients. The results of this study may provide a reference for developing novel biomarkers for endometriosis.

Supplementary material 1. Supplementary material 1. Supplementary material 2. Supplementary material 2. Supplementary material 3. Supplementary material 3. Supplementary material 4. Supplementary material 4.