Circulating miRNA as diagnostic tools for gynecological diseases and their applications in biosensor development

MicroRNAs (miRNAs) have emerged as robust biomarkers for diagnosing and prognosing gynecological diseases due to their disease-specific expression and remarkable stability in body fluids. Despite the inherent instability of RNA molecules, circulating miRNAs remain well protected through encapsulation in extracellular vesicles (EVs) or binding to RNA-binding proteins and lipoproteins, enabling reliable clinical detection. This review summarizes circulating miRNAs’ biogenesis and clinical relevance, emphasizing their roles in both malignant (e.g., ovarian and endometrial cancers) and benign (e.g., endometriosis and preeclampsia) conditions. Several electrochemical, fluorescent, and colorimetric biosensing platforms have been developed for sensitive and specific miRNA detection. However, most research focuses on cancer-associated miRNAs, leaving those linked to non-malignant diseases largely overlooked. To bridge this gap, this review highlights the need for broader exploration of underrepresented miRNAs and the development of multiplexed biosensing strategies to enhance diagnostic precision. Integrating advanced detection technologies with comprehensive biomarker discovery could significantly improve diagnostic accuracy, expand clinical applications, and accelerate the adoption of miRNA biosensors in point-of-care testing (POCT). Graphical abstract Overview of gynecologic disease biomarkers and their corresponding biosensing detection strategies. The schematic depicts the interrelationship between gynecological diseases, circulating miRNA biomarkers, and biosensor-based detection modalities. The inner circle highlights four representative conditions—ovarian cancer, endometrial cancer, endometriosis, and preeclampsia—whose onset and progression are closely associated with dysregulated serum or plasma miRNAs. Similar content being viewed by others Abbreviations - OC: - Ovarian cancer - EC: - Endometrial cancer - EM: - Endometriosis - PE: - Preeclampsia - EV: - Extracellular vesicles - POCT: - Point-of-care testing - HCR: - Hybridization chain reaction - CHA: - Catalytic hairpin assembly - TTT: - Target-triggered transcription - ECL: - Electrochemiluminescence - FRET: - Förster resonance energy transfer - CA-125: - Cancer antigen 125 - HE4: - Human epididymis protein 4 - FIGO: - International Federation of Gynecology and Obstetrics (Staging System) - AuNPs: - Gold nanoparticles - TMB: - 3,3′,5,5′-Tetramethylbenzidine - G4: - DNA G-quadruplex - FRA: - Fluorogenic RNA aptamer - MB: - Molecular beacon - CQD: - Carbon quantum dot - BHQ1: - Black Hole Quencher 1 - IUPAC: - International Union of Pure and Applied Chemistry

National Cancer Institute, S., Epidemiology, and End Results Program. Cancer Stat Facts: Ovarian Cancer. National Cancer Institute, 2025. https://seer.cancer.gov/statfacts/html/ovary.html Accessed 30 June 2025. Accorsi GS, Paiva LL, Schmidt R, Vieira M, Reis R, Andrade C. Sentinel Lymph Node Mapping vs Systematic Lymphadenectomy for Endometrial Cancer: Surgical Morbidity and Lymphatic Complications. J Minim Invasive Gynecol. 2020;27(4):938-945 e932. https://doi.org/10.1016/j.jmig.2019.07.030. (From NLM Medline). Smolarz B, Szyllo K, Romanowicz H. Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int J Mol Sci. 2021;22(19). https://doi.org/10.3390/ijms221910554 From NLM Medline. Christ JP, Yu O, Schulze-Rath R, Grafton J, Hansen K, Reed SD. Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015. Am J Obstet Gynecol. 2021;225(5):500 e501-500 e509. https://doi.org/10.1016/j.ajog.2021.06.067. (From NLM Medline). Jacobs I, Stabile I, Bridges J, Kemsley P, Reynolds C, Grudzinskas J, et al. Multimodal approach to screening for ovarian cancer. Lancet. 1988;1(8580):268–71. https://doi.org/10.1016/s0140-6736(88)90351-0. (From NLM Medline). Whitwell HJ, Worthington J, Blyuss O, Gentry-Maharaj A, Ryan A, Gunu R, et al. Improved early detection of ovarian cancer using longitudinal multimarker models. Br J Cancer. 2020;122(6):847–56. https://doi.org/10.1038/s41416-019-0718-9. (From NLM Medline). Simmons AR, Baggerly K, Bast RC Jr. The emerging role of HE4 in the evaluation of epithelial ovarian and endometrial carcinomas. Oncology (Williston Park). 2013;27(6):548–56 (From NLM Medline). Knific T, Osredkar J, Smrkolj S, Tonin I, Vouk K, Blejec A, et al. Novel algorithm including CA-125, HE4 and body mass index in the diagnosis of endometrial cancer. Gynecol Oncol. 2017;147(1):126–32. https://doi.org/10.1016/j.ygyno.2017.07.130. (From NLM Medline). Bostan IS, Mihaila M, Roman V, Radu N, Neagu MT, Bostan M, et al. Landscape of endometrial cancer: molecular mechanisms, biomarkers, and target therapy. Cancers (Basel). 2024. https://doi.org/10.3390/cancers16112027. (From NLM PubMed-not-MEDLINE). Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22. https://doi.org/10.1056/NEJMoa1414838. (From NLM Medline). Salvador S, Scott S, Glanc P, Eiriksson L, Jang JH, Sebastianelli A, et al. Guideline No. 403: Initial Investigation and Management of Adnexal Masses. J Obstet Gynaecol Can. 2020;42(8):1021-1029 e1023. https://doi.org/10.1016/j.jogc.2019.08.044. (From NLM Medline). Hakimian F, Ghourchian H, Hashemi AS, Arastoo MR, Behnam Rad M. Ultrasensitive optical biosensor for detection of miRNA-155 using positively charged Au nanoparticles. Sci Rep. 2018;8(1):2943. https://doi.org/10.1038/s41598-018-20229-z. (From NLM Medline). Cui M, Wang H, Yao X, Zhang D, Xie Y, Cui R, et al. Circulating microRNAs in cancer: potential and challenge. Front Genet. 2019;10:626. https://doi.org/10.3389/fgene.2019.00626. (From NLM PubMed-not-MEDLINE). Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004. https://doi.org/10.1038/sigtrans.2015.4. (From NLM PubMed-not-MEDLINE). Chen Y, Zhang L. Members of the microRNA-200 family are promising therapeutic targets in cancer. Exp Ther Med. 2017;14(1):10–7. https://doi.org/10.3892/etm.2017.4488. (From NLM PubMed-not-MEDLINE). Chirshev E, Oberg KC, Ioffe YJ, Unternaehrer JJ. Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med. 2019;8(1):24. https://doi.org/10.1186/s40169-019-0240-y. (From NLM PubMed-not-MEDLINE). Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, et al. Functional microrna involved in endometriosis. Mol Endocrinol. 2011;25(5):821–32. https://doi.org/10.1210/me.2010-0371. (From NLM Medline). Zhang L, Wang K, Wu Q, Jin L, Lu H, Shi Y, et al. Let-7 inhibits the migration and invasion of extravillous trophoblast cell via targeting MDM4. Mol Cell Probes. 2019;45:48–56. https://doi.org/10.1016/j.mcp.2019.05.002. (From NLM Medline). Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. https://doi.org/10.3322/caac.21834. (From NLM Medline). Vallen MJ, van der Steen SC, van Tilborg AA, Massuger LF, van Kuppevelt TH. Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: ʻwhen sweet turns sour’. Gynecol Oncol. 2014;135(2):371–81. https://doi.org/10.1016/j.ygyno.2014.08.023. (From NLM Medline). Huang J, Chan WC, Ngai CH, Lok V, Zhang L, Lucero-Prisno DE 3rd, et al. Worldwide burden, risk factors, and temporal trends of ovarian cancer: a global study. Cancers (Basel). 2022. https://doi.org/10.3390/cancers14092230. (From NLM PubMed-not-MEDLINE). Romero I, Leskela S, Mies BP, Velasco AP, Palacios J. Morphological and molecular heterogeneity of epithelial ovarian cancer: therapeutic implications. Eur J Cancer Suppl. 2020;15:1–15. https://doi.org/10.1016/j.ejcsup.2020.02.001. (From NLM PubMed-not-MEDLINE). Schmid G, Notaro S, Reimer D, Abdel-Azim S, Duggan-Peer M, Holly J, et al. Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer. BMC Cancer. 2016;16:102. https://doi.org/10.1186/s12885-016-2135-2. (From NLM Medline). Welponer H, Tsibulak I, Wieser V, Degasper C, Shivalingaiah G, Wenzel S, et al. The miR-34 family and its clinical significance in ovarian cancer. J Cancer. 2020;11(6):1446–56. https://doi.org/10.7150/jca.33831. (From NLM PubMed-not-MEDLINE). Taylor DD, Gercel-Taylor C. Retraction notice to "MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer" [Gynecologic Oncology, Volume 110, Issue 1, July 2008, Pages 13–21]. Gynecol Oncol 2023;175:192. https://doi.org/10.1016/j.ygyno.2023.06.002. From NLM PubMed-not-MEDLINE. Shapira I, Oswald M, Lovecchio J, Khalili H, Menzin A, Whyte J, et al. Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes. Br J Cancer. 2014;110(4):976–83. https://doi.org/10.1038/bjc.2013.795. (From NLM Medline). Takamizawa S, Kojima J, Umezu T, Kuroda M, Hayashi S, Maruta T, et al. miR-146a-5p and miR-191-5p as novel diagnostic marker candidates for ovarian clear cell carcinoma. Mol Clin Oncol. 2024;20(2):14. https://doi.org/10.3892/mco.2023.2712. (FromNLMPubMed-not-MEDLINE). Chao A, Lai CH, Chen HC, Lin CY, Tsai CL, Tang YH, et al. Serum microRNAs in clear cell carcinoma of the ovary. Taiwan J Obstet Gynecol. 2014;53(4):536–41. https://doi.org/10.1016/j.tjog.2014.07.005. (From NLM Medline). Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112(1):55–9. https://doi.org/10.1016/j.ygyno.2008.08.036. (From NLM Medline). Hausler SF, Keller A, Chandran PA, Ziegler K, Zipp K, Heuer S, et al. Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening. Br J Cancer. 2010;103(5):693–700. https://doi.org/10.1038/sj.bjc.6605833. (From NLM Medline). Kan CW, Hahn MA, Gard GB, Maidens J, Huh JY, Marsh DJ, et al. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer. BMC Cancer. 2012;12:627. https://doi.org/10.1186/1471-2407-12-627. (From NLM Medline). Meng X, Joosse SA, Muller V, Trillsch F, Milde-Langosch K, Mahner S, et al. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients. Br J Cancer. 2015;113(9):1358–66. https://doi.org/10.1038/bjc.2015.340. (From NLM Medline). Halvorsen AR, Kristensen G, Embleton A, Adusei C, Barretina-Ginesta MP, Beale P, et al. Evaluation of prognostic and predictive significance of circulating microRNAs in ovarian cancer patients. Dis Markers. 2017;2017:3098542. https://doi.org/10.1155/2017/3098542. (From NLM Medline). Pan C, Stevic I, Muller V, Ni Q, Oliveira-Ferrer L, Pantel K, et al. Exosomal microRNAs as tumor markers in epithelial ovarian cancer. Mol Oncol. 2018;12(11):1935–48. https://doi.org/10.1002/1878-0261.12371. (From NLM Medline). Zhang H, Xu S, Liu X. MicroRNA profiling of plasma exosomes from patients with ovarian cancer using high-throughput sequencing. Oncol Lett. 2019;17(6):5601–7. https://doi.org/10.3892/ol.2019.10220. (FromNLMPubMed-not-MEDLINE). Wang W, Yin Y, Shan X, Zhou X, Liu P, Cao Q, et al. The value of plasma-based microRNAs as diagnostic biomarkers for ovarian cancer. Am J Med Sci. 2019;358(4):256–67. https://doi.org/10.1016/j.amjms.2019.07.005. (From NLM Medline). Yokoi A, Yoshioka Y, Hirakawa A, Yamamoto Y, Ishikawa M, Ikeda SI, et al. A combination of circulating miRNAs for the early detection of ovarian cancer. Oncotarget. 2017;8(52):89811–23. https://doi.org/10.18632/oncotarget.20688. (From NLM PubMed-not-MEDLINE). Liu J, Yoo J, Ho JY, Jung Y, Lee S, Hur SY, et al. Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer. J Ovarian Res. 2021;14(1):59. https://doi.org/10.1186/s13048-021-00814-z. (From NLM Medline). Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660. (From NLM Medline). Zheng W, Yang J, Wang Y, Liu X. Exosomal miRNA-93 and miRNA-205 expression in endometrial cancer. J King Saud Univ Sci. 2020:32(1). https://doi.org/10.1016/j.jksus.2019.10.006. Yang X, Wang J. The role of metabolic syndrome in endometrial cancer: a review. Front Oncol. 2019;9:744. https://doi.org/10.3389/fonc.2019.00744. (From NLM PubMed-not-MEDLINE). Yang HP, Wentzensen N, Trabert B, Gierach GL, Felix AS, Gunter MJ, et al. Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study. Am J Epidemiol. 2013;177(2):142–51. https://doi.org/10.1093/aje/kws200. (From NLM Medline). Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M, Edwards RP, et al. Factors associated with type I and type II endometrial cancer. Cancer Causes Control. 2010;21(11):1851–6. https://doi.org/10.1007/s10552-010-9612-8. (From NLM Medline). Tsukamoto O, Miura K, Mishima H, Abe S, Kaneuchi M, Higashijima A, et al. Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma. Gynecol Oncol. 2014;132(3):715–21. https://doi.org/10.1016/j.ygyno.2014.01.029. (From NLM Medline). Ghazala RA, El-Attar EA, Abouzeid ZS. Circulating miRNA 27a and miRNA150-5p; a noninvasive approach to endometrial carcinoma. Mol Biol Rep. 2021;48(5):4351–60. https://doi.org/10.1007/s11033-021-06450-6. (From NLM Medline). Jia W, Wu Y, Zhang Q, Gao G, Zhang C, Xiang Y. Identification of four serum microRNAs from a genome-wide serum microRNA expression profile as potential non-invasive biomarkers for endometrioid endometrial cancer. Oncol Lett. 2013;6(1):261–7. https://doi.org/10.3892/ol.2013.1338. (From NLM PubMed-not-MEDLINE). Zhou L, Wang W, Wang F, Yang S, Hu J, Lu B, et al. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma. Mol Cancer. 2021;20(1):57. https://doi.org/10.1186/s12943-021-01352-4. (From NLM Medline). Fan X, Zou X, Liu C, Cheng W, Zhang S, Geng X, et al. Microrna expression profile in serum reveals novel diagnostic biomarkers for endometrial cancer. 2021. Biosci Rep. https://doi.org/10.1042/BSR20210111. (From NLM Medline). Torres A, Torres K, Pesci A, Ceccaroni M, Paszkowski T, Cassandrini P, et al. Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients. Int J Cancer. 2013;132(7):1633–45. https://doi.org/10.1002/ijc.27840. (From NLM Medline). Rostami S, Rounge TB, Pestarino L, Lyle R, Fortner RT, Haaland OA, et al. Differential levels of circulating RNAs prior to endometrial cancer diagnosis. Int J Cancer. 2024;155(5):946–56. https://doi.org/10.1002/ijc.34951. (From NLM Medline). Kong X, Xu X, Yan Y, Guo F, Li J, Hu Y, et al. Estrogen regulates the tumour suppressor miRNA-30c and its target gene, MTA-1, in endometrial cancer. PLoS ONE. 2014;9(3):e90810. https://doi.org/10.1371/journal.pone.0090810. (From NLM Medline). Boren T, Xiong Y, Hakam A, Wenham R, Apte S, Wei Z, et al. Micrornas and their target messenger RNAs associated with endometrial carcinogenesis. Gynecol Oncol. 2008;110(2):206–15. https://doi.org/10.1016/j.ygyno.2008.03.023. (From NLM Medline). Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2009;18(1):50–5. https://doi.org/10.1097/CEJ.0b013e328305a07a. (From NLM Medline). Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Prim. 2018;4(1):9. https://doi.org/10.1038/s41572-018-0008-5. Guo SW. Endometriosis and ovarian cancer: potential benefits and harms of screening and risk-reducing surgery. Fertil Steril. 2015;104(4):813–30. https://doi.org/10.1016/j.fertnstert.2015.08.006. (From NLM Medline). Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009. https://doi.org/10.1093/hropen/hoac009. (From NLM PubMed-not-MEDLINE). Cho S, Mutlu L, Grechukhina O, Taylor HS. Circulating microRNAs as potential biomarkers for endometriosis. Fertil Steril. 2015;103(5):1252-1260 e1251. https://doi.org/10.1016/j.fertnstert.2015.02.013. (From NLM Medline). Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ. Circulating micrornas identified in a genome-wide serum microrna expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab. 2013;98(1):281–9. https://doi.org/10.1210/jc.2012-2415. (From NLM Medline). Jia SZ, Yang Y, Lang J, Sun P, Leng J. Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. 2013;28(2):322–30. https://doi.org/10.1093/humrep/des413. (From NLM Medline). Cosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS. Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis. Fertil Steril. 2016;106(2):402–9. https://doi.org/10.1016/j.fertnstert.2016.04.013. (From NLM Medline). Chico-Sordo L, Ruiz-Martinez T, Toribio M, Gonzalez-Martin R, Spagnolo E, Dominguez F, et al. Identification of miR-30c-5p microRNA in serum as a candidate biomarker to diagnose endometriosis. Int J Mol Sci. 2024. https://doi.org/10.3390/ijms25031853. (From NLM Medline). Maged AM, Deeb WS, El Amir A, Zaki SS, El Sawah H, Al Mohamady M, et al. Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis. Int J Gynaecol Obstet. 2018;141(1):14–9. https://doi.org/10.1002/ijgo.12392. (From NLM Medline). Lin C, Zeng S, Li M. miR-424-5p combined with miR-17-5p has high diagnostic efficacy for endometriosis. Arch Gynecol Obstet. 2023;307(1):169–77. https://doi.org/10.1007/s00404-022-06492-6. (From NLM Medline). Bendifallah S, Dabi Y, Suisse S, Jornea L, Bouteiller D, Touboul C, Puchar A, Darai E. A Bioinformatics Approach to MicroRNA-Sequencing Analysis Based on Human Saliva Samples of Patients with Endometriosis. Int J Mol Sci. 2022;23(14). https://doi.org/10.3390/ijms23148045. From NLM Medline. Wang F, Wang H, Jin D, Zhang Y. Serum miR-17, IL-4, and IL-6 levels for diagnosis of endometriosis. Medicine (Baltimore). 2018;97(24):e10853. https://doi.org/10.1097/MD.0000000000010853. (From NLM Medline). Bashti O, Noruzinia M, Garshasbi M, Abtahi M. miR-31 and miR-145 as Potential Non-Invasive Regulatory Biomarkers in Patients with Endometriosis. Cell J. 2018;20(2):293. https://doi.org/10.22074/cellj.2018.5850. (From NLM PubMed-not-MEDLINE). Pateisky P, Pils D, Szabo L, Kuessel L, Husslein H, Schmitz A, et al. Hsa-miRNA-154-5p expression in plasma of endometriosis patients is a potential diagnostic marker for the disease. Reprod Biomed Online. 2018;37(4):449–66. https://doi.org/10.1016/j.rbmo.2018.05.007. (From NLM Medline). Brady P, Yousif A, Sasamoto N, Vitonis AF, Fendler W, Stawiski K, et al. Plasma microRNA expression in adolescents and young adults with endometriosis: the importance of hormone use. Front Reprod Health. 2024;6:1360417. https://doi.org/10.3389/frph.2024.1360417. (From NLM PubMed-not-MEDLINE). Walasik I, Klicka K, Grzywa TM, Szymusik I, Wlodarski P, Wielgos M, et al. Circulating miR-3613-5p but not miR-125b-5p, miR-199a-3p, and miR-451a are biomarkers of endometriosis. Reprod Biol. 2023;23(4):100796. https://doi.org/10.1016/j.repbio.2023.100796. (From NLM Medline). Rekker K, Saare M, Roost AM, Kaart T, Soritsa D, Karro H, et al. Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time. Fertil Steril. 2015;104(4):938-946 e932. https://doi.org/10.1016/j.fertnstert.2015.06.029. (From NLM Medline). Macedo TCC, Montagna E, Trevisan CM, Zaia V, de Oliveira R, Barbosa CP, et al. Prevalence of preeclampsia and eclampsia in adolescent pregnancy: a systematic review and meta-analysis of 291,247 adolescents worldwide since 1969. Eur J Obstet Gynecol Reprod Biol. 2020;248:177–86. https://doi.org/10.1016/j.ejogrb.2020.03.043. (From NLM Medline). Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43. https://doi.org/10.1161/HYPERTENSIONAHA.117.10803. (From NLM Medline). Mayor-Lynn K, Toloubeydokhti T, Cruz AC, Chegini N. Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci. 2011;18(1):46–56. https://doi.org/10.1177/1933719110374115. (From NLM Medline). Harapan H, Andalas M. The role of microRNAs in the proliferation, differentiation, invasion, and apoptosis of trophoblasts during the occurrence of preeclampsia systematic review. Tzu Chi Med J. 2015;27(2):54–64. https://doi.org/10.1016/j.tcmj.2015.05.001. Muralimanoharan S, Maloyan A, Mele J, Guo C, Myatt LG, Myatt L. MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. Placenta. 2012;33(10):816–23. https://doi.org/10.1016/j.placenta.2012.07.002. (From NLM Medline). Awamleh Z, Han VKM. Identification of miR-210-5p in human placentae from pregnancies complicated by preeclampsia and intrauterine growth restriction, and its potential role in the pregnancy complications. Pregnancy Hypertens. 2020;19:159–68. https://doi.org/10.1016/j.preghy.2020.01.002. (From NLM Medline). Zhu D, Guo T, Xu J, Yuan D, Lin M, Yang M. Elevated expression of miR-296 in human placentas and serum samples from pregnancies with preeclampsia. Br J Biomed Sci. 2023;80:11004. https://doi.org/10.3389/bjbs.2023.11004. (From NLM Medline). Gunel T, Kamali N, Hosseini MK, Gumusoglu E, Benian A, Aydinli K. Regulatory effect of miR-195 in the placental dysfunction of preeclampsia. J Matern Fetal Neonatal Med. 2020;33(6):901–8. https://doi.org/10.1080/14767058.2018.1508439. (From NLM Medline). Yang Q, Lu J, Wang S, Li H, Ge Q, Lu Z. Application of next-generation sequencing technology to profile the circulating microRNAs in the serum of preeclampsia versus normal pregnant women. Clin Chim Acta. 2011;412(23–24):2167–73. https://doi.org/10.1016/j.cca.2011.07.029. (From NLM Medline). Ura B, Feriotto G, Monasta L, Bilel S, Zweyer M, Celeghini C. Potential role of circulating microRNAs as early markers of preeclampsia. Taiwan J Obstet Gynecol. 2014;53(2):232–4. https://doi.org/10.1016/j.tjog.2014.03.001. (From NLM Medline). Sheikh AM, Small HY, Currie G, Delles C. Systematic review of micro-RNA expression in pre-eclampsia identifies a number of common pathways associated with the disease. PLoS ONE. 2016;11(8):e0160808. https://doi.org/10.1371/journal.pone.0160808. (From NLM Medline). Sandrim VC, Luizon MR, Palei AC, Tanus-Santos JE, Cavalli RC. Circulating microrna expression profiles in pre-eclampsia: evidence of increased miR-885-5p levels. BJOG. 2016;123(13):2120–8. https://doi.org/10.1111/1471-0528.13903. (From NLM Medline). Akgor U, Ayaz L, Cayan F. Expression levels of maternal plasma microRNAs in preeclamptic pregnancies. J Obstet Gynaecol. 2021;41(6):910–4. https://doi.org/10.1080/01443615.2020.1820465. (From NLM Medline). Sheng C, Zhao Y, Zhu L. Down-regulation of EDN1 gene expression by circulating miR-206 is associated with risk of preeclampsia. Medicine (Baltimore). 2020;99(22):e20319. https://doi.org/10.1097/MD.0000000000020319. (From NLM Medline). Pineles BL, Romero R, Montenegro D, Tarca AL, Han YM, Kim YM, et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol. 2007;196(3):261 e261-266. https://doi.org/10.1016/j.ajog.2007.01.008. (From NLM Medline). Wu L, Zhou H, Lin H, Qi J, Zhu C, Gao Z, et al. Circulating microRNAs are elevated in plasma from severe preeclamptic pregnancies. Reproduction. 2012;143(3):389–97. https://doi.org/10.1530/REP-11-0304. (From NLM Medline). Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, et al. miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells. 2020;9(2):276. https://doi.org/10.3390/cells9020276. Kirian RD, Steinman D, Jewell CM, Zierden HC. Extracellular vesicles as carriers of mRNA: opportunities and challenges in diagnosis and treatment. Theranostics. 2024;14(5):2265–89. https://doi.org/10.7150/thno.93115. Ouyang T, Liu Z, Han Z, Ge Q. Microrna detection specificity: recent advances and future perspective. Anal Chem. 2019;91(5):3179–86. https://doi.org/10.1021/acs.analchem.8b05909. (From NLM Medline). Moldovan L, Batte KE, Trgovcich J, Wisler J, Marsh CB, Piper M. Methodological challenges in utilizing miRNAs as circulating biomarkers. J Cell Mol Med. 2014;18(3):371–90. https://doi.org/10.1111/jcmm.12236. (From NLM Medline). Xu D, Di K, Fan B, Wu J, Gu X, Sun Y, et al. Micrornas in extracellular vesicles: sorting mechanisms, diagnostic value, isolation, and detection technology. Front Bioeng Biotechnol. 2022;10:948959. https://doi.org/10.3389/fbioe.2022.948959. (From NLM PubMed-not-MEDLINE). Cissell KA, Shrestha S, Deo SK. MicroRNA detection: challenges for the analytical chemist. Anal Chem. 2007;79(13):4754–61. https://doi.org/10.1021/ac0719305. Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the MicroRNA spectrum between serum and plasma. PLoS ONE. 2012;7(7):e41561. https://doi.org/10.1371/journal.pone.0041561. (From NLM Medline). Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8. https://doi.org/10.1073/pnas.0804549105. (From NLM Medline). He Y, Chevillet JR, Liu G, Kim TK, Wang K. The effects of microRNA on the absorption, distribution, metabolism and excretion of drugs. Br J Pharmacol. 2015;172((11)):2733–47. https://doi.org/10.1111/bph.12968. (From NLM Medline). DeLucas M, Sanchez J, Palou A, Serra F. The impact of diet on miRNA regulation and its implications for health: a systematic review. Nutrients. 2024. https://doi.org/10.3390/nu16060770. (From NLM Medline). Hu Z, Shen WJ, Cortez Y, Tang X, Liu LF, Kraemer FB, et al. Hormonal regulation of microRNA expression in steroid producing cells of the ovary, testis and adrenal gland. PLoS ONE. 2013;8(10):e78040. https://doi.org/10.1371/journal.pone.0078040. (From NLM Medline). De Guire V, Robitaille R, Tetreault N, Guerin R, Menard C, Bambace N, et al. Circulating miRNAs as sensitive and specific biomarkers for the diagnosis and monitoring of human diseases: promises and challenges. Clin Biochem. 2013;46(10–11):846–60. https://doi.org/10.1016/j.clinbiochem.2013.03.015. (From NLM Medline). Jet T, Gines G, Rondelez Y, Taly V. Advances in multiplexed techniques for the detection and quantification of microRNAs. Chem Soc Rev. 2021;50(6):4141–61. https://doi.org/10.1039/d0cs00609b. (From NLM Medline). Shami-Shah A, Travis BG, Walt DR. Advances in extracellular vesicle isolation methods: a path towards cell-type specific EV isolation. Extracell Vesicles Circ Nucleic Acids. 2023;4(3):447–60. https://doi.org/10.20517/evcna.2023.14. (From NLM PubMed-not-MEDLINE). Greytak SR, Engel KB, Hoon DSB, Elias KM, Lockwood CM, Guan P, et al. Evidence-based procedures to improve the reliability of circulating miRNA biomarker assays. Clin Chem Lab Med. 2024;62(1):60–6. https://doi.org/10.1515/cclm-2023-0131. (From NLM Medline). Ma C, Zhang Y, Ding R, Chen H, Wu X, Xu L, et al. In search of the ratio of miRNA expression as robust biomarkers for constructing stable diagnostic models among multi-center data. Front Genet. 2024;15:1381917. https://doi.org/10.3389/fgene.2024.1381917. (From NLM PubMed-not-MEDLINE). Moga MA, Balan A, Dimienescu OG, Burtea V, Dragomir RM, Anastasiu CV. Circulating miRNAs as Biomarkers for Endometriosis and Endometriosis-Related Ovarian Cancer-An Overview. J Clin Med 2019;8(5). https://doi.org/10.3390/jcm8050735. From NLM PubMed-not-MEDLINE. Kim SW, Li Z, Moore PS, Monaghan AP, Chang Y, Nichols M, et al. A sensitive non-radioactive northern blot method to detect small RNAs. Nucleic Acids Res. 2010;38(7):e98. https://doi.org/10.1093/nar/gkp1235. (From NLM Medline). Wang B, Xi Y. Challenges for microrna microarray data analysis. Microarrays. 2013;2(2):34–50. https://doi.org/10.3390/microarrays2020034. (From NLM PubMed-not-MEDLINE). Farazi TA, Horlings HM, Ten Hoeve JJ, Mihailovic A, Halfwerk H, Morozov P, et al. Microrna sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011;71(13):4443–53. https://doi.org/10.1158/0008-5472.CAN-11-0608. Forero DA, Gonzalez-Giraldo Y, Castro-Vega LJ, Barreto GE. QPCR-based methods for expression analysis of miRNAs. Biotechniques. 2019;67(4):192–9. https://doi.org/10.2144/btn-2019-0065. (From NLM Medline). Chandrasekaran AR, Punnoose JA, Zhou L, Dey P, Dey BK, Halvorsen K. DNA nanotechnology approaches for microRNA detection and diagnosis. Nucleic Acids Res. 2019;47(20):10489–505. https://doi.org/10.1093/nar/gkz580. (From NLM Medline). Hua Y, Ma J, Li D, Wang R. DNA-based biosensors for the biochemical analysis: a review. Biosensors. 2022. https://doi.org/10.3390/bios12030183. (From NLM Medline). Wei Z, Wang X, Feng H, Ji F, Bai D, Dong X, et al. Isothermal nucleic acid amplification technology for rapid detection of virus. Crit Rev Biotechnol. 2023;43(3):415–32. https://doi.org/10.1080/07388551.2022.2030295. (From NLM Medline). Glokler J, Lim TS, Ida J, Frohme M. Isothermal amplifications - a comprehensive review on current methods. Crit Rev Biochem Mol Biol. 2021;56(6):543–86. https://doi.org/10.1080/10409238.2021.1937927. (From NLM Medline). Wang Y, Feng H, Huang K, Quan J, Yu F, Liu X, et al. Target-triggered hybridization chain reaction for ultrasensitive dual-signal miRNA detection. Biosens Bioelectron. 2022;215:114572. https://doi.org/10.1016/j.bios.2022.114572. (From NLM Medline). Liu J, Zhang Y, Xie H, Zhao L, Zheng L, Ye H. Applications of Catalytic Hairpin Assembly Reaction in Biosensing. Small. 2019;15(42):e1902989. https://doi.org/10.1002/smll.201902989. (From NLM Medline). Sun M, Liu B, Li T, Li C, Duan WJ, Xie B, et al. A universal rolling circle amplification for label-free and highly specific nucleic acid sensing. Chem Commun (Camb). 2022;58(84):11863–6. https://doi.org/10.1039/d2cc04058a. (From NLM Medline). Reid MS, Le XC, Zhang H. Exponential isothermal amplification of nucleic acids and assays for proteins, cells, small molecules, and enzyme activities: an EXPAR example. Angew Chem Int Ed Engl. 2018;57(37):11856–66. https://doi.org/10.1002/anie.201712217. (From NLM Medline). Cao X, Chen C, Zhu Q. Biosensors based on functional nucleic acids and isothermal amplification techniques. Talanta. 2023;253:123977. https://doi.org/10.1016/j.talanta.2022.123977. Chiorcea-Paquim AM. Advances in electrochemical biosensor technologies for the detection of nucleic acid breast cancer biomarkers. Sensors (Basel). 2023. https://doi.org/10.3390/s23084128. (From NLM Medline). El-Gammal MA, Sayed FE, Allam NK. Comprehensive analysis of electrochemical biosensors for early ovarian cancer detection. RSC Adv. 2024;14(50):37580–97. https://doi.org/10.1039/d4ra05972g. (From NLM PubMed-not-MEDLINE). Labuda J, Brett AMO, Evtugyn G, Fojta M, Mascini M, Ozsoz M, et al. Electrochemical nucleic acid-based biosensors: Concepts, terms, and methodology (IUPAC Technical Report). Pure Appl Chem. 2010;82(5):1161–87. https://doi.org/10.1351/PAC-REP-09-09-01. Rouhi S, Ghasemi H, Alizadeh M, Movahedpour A, Vahedi F, Fattahi M, et al. MiRNA-based electrochemical biosensors for ovarian cancer. Clin Chim Acta. 2025;564:119946. https://doi.org/10.1016/j.cca.2024.119946. (From NLM Medline). Wang C, Chen M, Han Q, Wu J, Zhao X, Fu Y. A three-dimensional DNA nanomachine with target recycling amplification technology and multiple electrochemiluminescence resonance energy transfer for sensitive microRNA-141 detection. Biosens Bioelectron. 2020;156:112146. https://doi.org/10.1016/j.bios.2020.112146. (From NLM Medline). Zhang Z, Zhang L, Wang Y, Yao J, Wang T, Weng Z, et al. Ultrasensitive electrochemical biosensor for attomolar level detection of let 7a based on toehold mediated strand displacement reaction circuits and molecular beacon mediated circular strand displacement polymerization. Anal Chim Acta. 2021;1147:108–15. https://doi.org/10.1016/j.aca.2020.12.057. (From NLM Medline). Shabaninejad Z, Yousefi F, Movahedpour A, Ghasemi Y, Dokanehiifard S, Rezaei S, et al. Electrochemical-based biosensors for microRNA detection: nanotechnology comes into view. Anal Biochem. 2019;581:113349. https://doi.org/10.1016/j.ab.2019.113349. (From NLM Medline). Park Y, Lee CY, Kang S, Kim H, Park KS, Park HG. Universal, colorimetric microrna detection strategy based on target-catalyzed toehold-mediated strand displacement reaction. Nanotechnology. 2018;29(8):085501. https://doi.org/10.1088/1361-6528/aaa3a3. (From NLM Medline). Lee J, Na HK, Lee S, Kim WK. Advanced graphene oxide-based paper sensor for colorimetric detection of miRNA. Mikrochim Acta. 2021;189(1):35. https://doi.org/10.1007/s00604-021-05140-1. (From NLM Medline). He Z, Yin H, Chang CC, Wang G, Liang X. Interfacing DNA with gold nanoparticles for heavy metal detection. Biosensors. 2020. https://doi.org/10.3390/bios10110167. (From NLM Medline). Hu X, Zhang Y, Ding T, Liu J, Zhao H. Multifunctional gold nanoparticles: a novel nanomaterial for various medical applications and biological activities. Front Bioeng Biotechnol. 2020;8:990. https://doi.org/10.3389/fbioe.2020.00990. (From NLM PubMed-not-MEDLINE). Tu LP. Gold nanomaterials for biochemical sensing. Gold Bulletin. 2022;55(2):169–85. https://doi.org/10.1007/s13404-022-00304-1. Wang C, Zhang Y, Liu C, Gou S, Hu S, Guo W. A portable colorimetric point-of-care testing platform for microRNA detection based on programmable entropy-driven dynamic DNA network modulated DNA-gold nanoparticle hybrid hydrogel film. Biosens Bioelectron. 2023;225:115073. https://doi.org/10.1016/j.bios.2023.115073. (From NLM Medline). Yao Y, Long C, Gao Z, Cheng Y, Chen S, Liu Q, et al. Magnetic three-dimensional ordered DNA arrays for colorimetric detection of dual-miRNAs based on molecular logic gate. Sensors and Actuators B: Chemical. 2025;445:138545. https://doi.org/10.1016/j.snb.2025.138545. Qu H, Fan C, Chen M, Zhang X, Yan Q, Wang Y, et al. Recent advances of fluorescent biosensors based on cyclic signal amplification technology in biomedical detection. J Nanobiotechnology. 2021;19(1):403. https://doi.org/10.1186/s12951-021-01149-z. (From NLM Medline). Nawrot W, Drzozga K, Baluta S, Cabaj J, Malecha K. A fluorescent biosensors for detection vital body fluids’ agents. Sensors (Basel). 2018. https://doi.org/10.3390/s18082357. (From NLM Medline). Strianese M, Staiano M, Ruggiero G, Labella T, Pellecchia C, D’Auria S. Fluorescence-based biosensors. Methods Mol Biol. 2012;875:193–216. https://doi.org/10.1007/978-1-61779-806-1_9. (From NLM Medline). Xue T, Bongu SR, Huang H, Liang W, Wang Y, Zhang F, et al. Ultrasensitive detection of microRNA using a bismuthene-enabled fluorescence quenching biosensor. Chem Commun (Camb). 2020;56(51):7041–4. https://doi.org/10.1039/d0cc01004a. (From NLM Medline). Guoshuai J, Xiaomeng X, Zengdan G, Xingxing H, Qi P, Hanbing Z, et al. A rapid and high sensitivity RNA detection based on NASBA and G4-ThT fluorescent biosensor. Sci Rep. 2022;12(1):10076. https://doi.org/10.1038/s41598-022-14107-y. (From NLM Medline). Qaddare SH, Salimi A. Amplified fluorescent sensing of DNA using luminescent carbon dots and AuNPs/GO as a sensing platform: A novel coupling of FRET and DNA hybridization for homogeneous HIV-1 gene detection at femtomolar level. Biosens Bioelectron. 2017;89(Pt 2):773–80. https://doi.org/10.1016/j.bios.2016.10.033. (From NLM Medline). Zhang X, Hu Y, Yang X, Tang Y, Han S, Kang A, et al. FÖrster resonance energy transfer (FRET)-based biosensors for biological applications. Biosens Bioelectron. 2019;138:111314. https://doi.org/10.1016/j.bios.2019.05.019. (From NLM Medline). Chen X, Xu K, Li J, Yang M, Li X, Chen Q, et al. Switch-conversional ratiometric fluorescence biosensor for miRNA detection. Biosens Bioelectron. 2020;155:112104. https://doi.org/10.1016/j.bios.2020.112104. (From NLM Medline). Mahani M, Mousapour Z, Divsar F, Nomani A, Ju H. A carbon dot and molecular beacon based fluorometric sensor for the cancer marker microRNA-21. Mikrochim Acta. 2019;186(3):132. https://doi.org/10.1007/s00604-019-3233-z. (From NLM Medline). Park Y, Yoon J, Lee J, Lee S, Park HG. Multiplexed miRNA detection based on target-triggered transcription of multicolor fluorogenic RNA aptamers. Biosens Bioelectron. 2022;204:114071. https://doi.org/10.1016/j.bios.2022.114071. (From NLM Medline). Huang L, Zhang L, Chen X. Updated review of advances in microRNAs and complex diseases: taxonomy, trends and challenges of computational models. Brief Bioinform. 2022. https://doi.org/10.1093/bib/bbac358. (From NLM Medline). Pimalai D, Putnin T, Waiwinya W, Chotsuwan C, Aroonyadet N, Japrung D. Development of electrochemical biosensors for simultaneous multiplex detection of microRNA for breast cancer screening. Mikrochim Acta. 2021;188(10):329. https://doi.org/10.1007/s00604-021-04995-8. (From NLM Medline). Wen Y, Wang LP, Wang JH, Yu YL, Chen S. Computer-aided design of 3D non-enzymatic catalytic cascade systems for in situ multiplexed mRNA imaging in single-cells. Anal Chem. 2025;97(7):4176–84. https://doi.org/10.1021/acs.analchem.4c06589. (From NLM Medline). Ak MF. A comparative analysis of breast cancer detection and diagnosis using data visualization and machine learning applications. Healthcare. 2020. https://doi.org/10.3390/healthcare8020111. (From NLM PubMed-not-MEDLINE). Kumar A, Parihar A, Panda U, Parihar DS. Microfluidics-based point-of-care testing (POCT) devices in dealing with waves of COVID-19 pandemic: the emerging solution. ACS Appl Bio Mater. 2022;5(5):2046–68. https://doi.org/10.1021/acsabm.1c01320. (From NLM Medline). Rasmi Y, Li X, Khan J, Ozer T, Choi JR. Emerging point-of-care biosensors for rapid diagnosis of COVID-19: current progress, challenges, and future prospects. Anal Bioanal Chem. 2021;413(16):4137–59. https://doi.org/10.1007/s00216-021-03377-6. (From NLM Medline). Amiri M, Afshary H, Bezaatpour A, Hatamikia S, Wei J, Boukherroub R, et al. A critical review on neurodegenerative biomarker diagnostics: where is the field heading to? Anal Bioanal Chem. 2025. https://doi.org/10.1007/s00216-025-06061-1. (From NLM Publisher). Manoharan Nair Sudha Kumari S, Thankappan Suryabai X. Sensing the future-frontiers in biosensors: exploring classifications, principles, and recent advances. ACS Omega. 2024;9(50):48918–87. https://doi.org/10.1021/acsomega.4c07991. (From NLM PubMed-not-MEDLINE). Ravi N, Cortade DL, Ng E, Wang SX. Diagnostics for SARS-CoV-2 detection: a comprehensive review of the FDA-EUA COVID-19 testing landscape. Biosens Bioelectron. 2020;165:112454. https://doi.org/10.1016/j.bios.2020.112454. (From NLM Medline). Moazampour M, Zare HR, Shekari Z. Femtomolar determination of an ovarian cancer biomarker (miR-200a) in blood plasma using a label free electrochemical biosensor based on L-cysteine functionalized ZnS quantum dots. Anal Methods. 2021;13(17):2021–9. https://doi.org/10.1039/d1ay00330e. (From NLM Medline). Wang F, Liu Y, Zhang L, Zhang Z, Huang C, Zang D, et al. Photoelectrochemical biosensor based on CdS quantum dots anchored h-BN nanosheets and tripodal DNA walker for sensitive detection of miRNA-141. Anal Chim Acta. 2022;1226:340265. https://doi.org/10.1016/j.aca.2022.340265. (From NLM Medline). Li YX, Wang QX, Wang YL. Direct and accurate miRNA detection based on CRISPR/Cas13a-triggered exonuclease-iii-assisted colorimetric assay. J Anal Sci Technol. 2024;15(1):21. https://doi.org/10.1186/s40543-024-00434-4. Zheng Y, Chen J, Li Y, Xu Y, Chen L, Chen W, et al. Dual-probe fluorescent biosensor based on T7 exonuclease-assisted target recycling amplification for simultaneous sensitive detection of microRNA-21 and microRNA-155. Anal Bioanal Chem. 2021;413(6):1605–14. https://doi.org/10.1007/s00216-020-03121-6. (From NLM Medline). Cirillo PDR, Margiotti K, Mesoraca A, Giorlandino C. Quantification of circulating microRNAs by droplet digital PCR for cancer detection. BMC Res Notes. 2020;13(1):351. https://doi.org/10.1186/s13104-020-05190-3. (From NLM Medline). Skryabin GO, Komelkov AV, Zhordania KI, Bagrov DV, Vinokurova SV, Galetsky SA, et al. Extracellular vesicles from uterine aspirates represent a promising source for screening markers of gynecologic cancers. Cells. 2022. https://doi.org/10.3390/cells11071064. (From NLM Medline). Vergauwen G, Tulkens J, Pinheiro C, Avila Cobos F, Dedeyne S, De Scheerder MA, et al. Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions. J Extracell Vesicles. 2021;10(10):e12122. https://doi.org/10.1002/jev2.12122. (From NLM Medline). Pandey R, Woo HH, Varghese F, Zhou M, Chambers SK. Circulating miRNA profiling of women at high risk for ovarian cancer. Transl Oncol. 2019;12(5):714–25. https://doi.org/10.1016/j.tranon.2019.01.006. (From NLM PubMed-not-MEDLINE). Vigneron N, Meryet-Figuiere M, Guttin A, Issartel JP, Lambert B, Briand M, et al. Towards a new standardized method for circulating miRNAs profiling in clinical studies: interest of the exogenous normalization to improve miRNA signature accuracy. Mol Oncol. 2016;10(7):981–92. https://doi.org/10.1016/j.molonc.2016.03.005. (From NLM Medline). Ji T, Zheng ZG, Wang FM, Xu LJ, Li LF, Cheng QH, et al. Differential microRNA expression by solexa sequencing in the sera of ovarian cancer patients. Asian Pac J Cancer Prev. 2014;15(4):1739–43. https://doi.org/10.7314/apjcp.2014.15.4.1739. (From NLM Medline). Al-Showimi M, Al-Yousef N, Alharbi W, Alkhezayem S, Almalik O, Alhusaini H, et al. Microrna-126 expression in the peripheral white blood cells of patients with breast and ovarian cancer is a potential biomarker for the early prediction of cancer risk in the carriers of methylated BRCA1. Oncol Lett. 2022;24(2):276. https://doi.org/10.3892/ol.2022.13396. (From NLM PubMed-not-MEDLINE). Wang W, Wu LR, Li C, Zhou X, Liu P, Jia X, et al. Five serum microRNAs for detection and predicting of ovarian cancer. Eur J Obstet Gynecol Reprod Biol: X. 2019;3:100017. https://doi.org/10.1016/j.eurox.2019.100017. (From NLM PubMed-not-MEDLINE). Mollinedo F. Neutrophil degranulation, plasticity, and cancer metastasis. Trends Immunol. 2019;40(3):228–42. https://doi.org/10.1016/j.it.2019.01.006. (From NLM Medline). Wang W, Jo H, Park S, Kim H, Kim SI, Han Y, et al. Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer. Cancer Lett. 2022;542:215735. https://doi.org/10.1016/j.canlet.2022.215735. (From NLM Medline). Su YY, Sun L, Guo ZR, Li JC, Bai TT, Cai XX, et al. Upregulated expression of serum exosomal miR-375 and miR-1307 enhance the diagnostic power of CA125 for ovarian cancer. J Ovarian Res. 2019;12(1):6. https://doi.org/10.1186/s13048-018-0477-x. (From NLM Medline). de Araujo WR, Lukas H, Torres MDT, Gao W, de la Fuente-Nunez C. Low-cost biosensor technologies for rapid detection of COVID-19 and future pandemics. ACS Nano. 2024;18(3):1757–77. https://doi.org/10.1021/acsnano.3c01629. (From NLM Medline). Wang ZY, Sun MH, Zhang Q, Li PF, Wang K, Li XM. Advances in point-of-care testing of microRNAs based on portable instruments and visual detection. Biosensors. 2023;13(7):747. https://doi.org/10.3390/bios13070747. (From NLM Medline). Onisor D, Brusnic O, Banescu C, Carstea C, Sasaran M, Stoian M, et al. MiR-155 and miR-21 as diagnostic and therapeutic biomarkers for ulcerative colitis: there is still a long way to go. Biomedicines. 2024. https://doi.org/10.3390/biomedicines12061315. (From NLM PubMed-not-MEDLINE). Author information Authors and Affiliations Contributions Yu-Ling Wu: conceptualization, formal analysis, visualization, writing—original draft. Hsu-Ching Yen: conceptualization, formal analysis, visualization, writing—original draft. Yi-Hsuan Chen: formal analysis, writing—original draft. Leo Yang: writing—original draft. Pao-Ling Torng: conceptualization, supervision, writing—review and editing. Ja-an Annie Ho: conceptualization, funding acquisition, project administration, supervision, writing—review and editing. Corresponding authors Ethics declarations Conflict of interest All authors declare that they have no known competing financial or nonfinancial interests that could have appeared to influence the work reported in this paper. Ja-an Annie Ho is a member of ABC’s International Advisory Board but was not involved in the peer review of this paper. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Published in the topical collection featuring Promising Early-Career (Bio)Analytical Researchers in 2026 with guest editors Antje J. Baeumner, Soledad Cárdenas, and Alberto Cavazzini. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Wu, YL., Yen, HC., Chen, YH. et al. Circulating miRNA as diagnostic tools for gynecological diseases and their applications in biosensor development. Anal Bioanal Chem 418, 533–557 (2026). https://doi.org/10.1007/s00216-025-06196-1 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00216-025-06196-1