Abstract
Objectives
To evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC).
Patients and methods
Exosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot.
Results
The expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899–0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875–0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively.
Conclusion
Our data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.
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Introduction
Ovarian cancer (OC) is a leading death cause for gynecological cancers, characterized by poor prognosis and high mortality rates. The most prevalent type of ovarian cancer is epithelial ovarian cancer (EOC), accounting for 90% of cases. EOC originates from the flat surface epithelial cells that cover the ovary, subserosal inclusion cysts, or the fimbriated end of the fallopian tubes [1]. Unfavorable outcomes in OC are mainly attributed to late-stage diagnosis, with an overall 5-year survival rate below 30% [2]. Conversely, early-stage boasts a 5-year survival rate exceeding 90%, highlighting the potential for improved prognoses through accurate early-stage diagnosis. Presently, serum cancer antigen 125 (CA125) test and transvaginal ultrasonography (TVUS) are commonly used screening tools for OC [3]. However, they often fail to detect OC at earlier stage, leading to limited reduction in OC-related mortality. Notably, only 50–60% of stage I-II OC patients exhibit increased CA125 levels [4]. Consequently, there is an urgent need for novel diagnostic markers to identify early-stage OC.
Exosomes are small membranous particles (40–160 nm), which are released into the extracellular space through the fusion of multivesicular bodies with the cell membrane [5]. They transmit functionally informative molecules, including proteins, nucleic acids, lipids, and even organelles into recipient cells to mediate intercellular communications [6]. Exosomes can be found in various body fluids, such as blood, urine, and cerebrospinal fluid. Accumulating evidence suggests that exosomes play fundamental roles in the progression, metastasis, and drug resistance of OC [7, 8]. MicroRNAs (miRNAs) are one of most abundant types in the RNA cargo of exosomes [9]. Exosomal miRNAs are usually tumor specific [10], thus attracting increasing attention in cancer diagnosis and prognosis due to their non-invasiveness, easy accessibility and stability [11]. For instance, plasma levels of exosomal miR-139-3p may serve as a novel biomarker for the early diagnosis and metastasis monitoring in colorectal cancer [12]. Plasma exosomes of breast cancer patients show selective enrichment of miR-1246, which is significantly increased compared to healthy controls [13].MiR-223, a multifunctional miRNA, plays a central role in innate immunity, including regulating immune cell differentiation and macrophage polarization, it also has immunomodulatory effects in certain tissues [14]. Recently, numerous studies have reported that miR-223 is involved in the development of varius types of cancer including hepatocellular [15], gastro-esophageal [16], breast [17] and lung cancers [ Plasma exosomal miR-223 was significantly up-regulated in EOC patients and correlated with disease progression. Our study clearly demonstrates that exosomal miR-223, as a non-invasive biomarker, may complement CA125 to enhance the diagnostic accuracy for differentiating early-stage EOC from healthy subjects.Conclusion
Availability of data and materials
The data used and/or analyzed during the current study are available from the corresponding author.
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Funding
This study was supported by Tangshan Talent Funding Project (A202010008) and Tangshan Talent Funding Project A202010008 (C202303032).
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ZY: Conceptualization, and Writing—original draft. LY: Formal analysis; ZL: Investigation; NQ and LT: Methodology; All authors have read and agreed to the published version of the manuscript.
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The present study was approved by the institutional research ethics committee of Tangshan ’Workers’ Hospital. Informed consent was obtained from each participant.
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Yang, L., Yang, Z., Liu, Z. et al. Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer. BMC Women's Health 24, 150 (2024). https://doi.org/10.1186/s12905-024-02976-6
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DOI: https://doi.org/10.1186/s12905-024-02976-6