As an aggressive tumor, ovarian cancer poses a serious threat to women's health. Because the early symptoms are not obvious, many patients are diagnosed at an advanced stage, and the treatment response is limited, and the prognosis is poor. Although the current detection methods for ovarian cancer include serum tumor marker detection and imaging examination, these methods have certain limitations, such as insufficient sensitivity and specificity, or limited ability to identify early-stage tumors. In recent years, microRNAs (miRNAs), as a class of non-coding RNA molecules, have shown great potential as biomarkers for early detection due to their regulatory role in tumorigenesis and development, and their role in early diagnosis, treatment response evaluation and prognosis judgment of ovarian cancer has been increasingly emphasized. Recently, a review paper was published in the journal Frontiers in Molecular Biosciences discussing the potential of miRNAs as biomarkers for the early detection of ovarian cancer [1]. This article summarizes the core content of the research for the benefit of readers.
The role of miRNAs in ovarian cancer detection
MicroRNAs (miRNAs) are a class of non-coding RNA molecules with a length of approximately 22 nucleotides that are involved in a variety of biological processes by regulating gene expression within cells [2]. Aberrant expression of miRNAs is closely related to the biological behavior of tumors, and they play a key role in tumor initiation, progression, metastasis, and response to treatment [3]. These small molecules are considered to be promising biomarkers for early detection of ovarian cancer due to their specific expression patterns in tumor tissues.
miRNAs have significant advantages as biomarkers for ovarian cancer. They are stable in the patient's blood and body fluids and can be detected non-invasively, providing patients with a gentler means of monitoring [4]. Compared with traditional tumor markers, miRNAs have demonstrated higher sensitivity and specificity in the diagnosis of ovarian cancer, enabling early detection of disease (Table 1) [4-11]. In addition, miRNA expression patterns vary at different stages of the disease, providing unique molecular information for disease staging, treatment efficacy assessment, and prognosis (Table 2) [4,12-22].
Table 1 Diagnostic significance of miRNAs in ovarian cancer
Table 2 Significance of miRNAs in the prognosis of ovarian cancer
miRNA detection technology
The detection technology of miRNA is the key to its application in the early diagnosis of ovarian cancer. Currently, a variety of miRNA detection technologies have been developed and optimized to suit different research and clinical needs [23]. Among them, quantitative real-time polymerase chain reaction (qRT-PCR) is a commonly used method for miRNA quantification, which is widely recognized for its high sensitivity and specificity. Although qRT-PCR requires specific fluorescently labeled probes and may increase costs, it enables precise measurement of expression levels of specific miRNAs [24].
Northern blotting is another traditional miRNA detection method that is quantified by molecular hybridization and gel electrophoresis. Although Northern blotting is capable of detecting the size of mature miRNAs, it requires a large amount of starting material and is cumbersome, limiting its application in high-throughput studies [25]. Microarray technology is capable of monitoring the expression of thousands of miRNAs simultaneously and is characterized by high throughput, but may be affected by cross-breeding between homologous miRNA sequences, which can reduce the specificity of the assay [26].
RNA sequencing technologies, especially next-generation sequencing (NGS), provide deeper insights into the analysis of miRNAs. NGS technology is able to provide detailed information on miRNA expression and variation, but its complex workflow and possible bias require careful experimental design and data processing to overcome [27].
In addition to the above methods, biosensor-based miRNA detection has attracted attention due to its rapidity, sensitivity, and specificity. For example, silicon nanowire-based biosensors are capable of detecting miRNA biomarkers associated with ovarian cancer with high sensitivity and low detection limits [28]. Microfluidic technology combined with digital PCR (dPCR) provides a new platform for miRNA quantification, which enables high-efficiency detection of miRNA through an integrated system [29].
Fluorescence miRNA detection utilizes a toehold-mediated strand replacement (TMSD) reaction, providing a PCR-independent assay. This method quantifies miRNA by changes in the intensity of the fluorescence signal, which has the advantage of being fast and cost-effective [30]. The CRISPR/Cas system has also been used for miRNA detection, enabling highly specific detection of specific miRNAs through specific guide RNAs (gRNAs) and Cas protein complexes [31].
Research progress of miRNAs as biomarkers of ovarian cancer
miRNAs are playing an increasingly important role in the field of ovarian cancer research. They are not only involved in the occurrence and progression of ovarian cancer, but also the changes in their expression patterns provide new perspectives for disease diagnosis, prognosis assessment, and personalized treatment. With a better understanding of miRNA function, a series of studies have revealed the aberrant expression of specific miRNAs in ovarian cancer and explored their potential as biomarkers.
In the early diagnosis of ovarian cancer, miRNAs have shown great application prospects. For example, miR-200 family members have significantly different expression levels in ovarian cancer tissues compared to normal ovarian epithelial cells, suggesting that they may play an inhibitory role in tumorigenesis [32]. In addition, miRNAs such as miR-21 and miR-155 are significantly elevated in serum in ovarian cancer patients, which opens up the possibility of noninvasive blood-based testing [33].
miRNAs are also of great value in the prognostic assessment of ovarian cancer. Specific miRNA expression patterns are closely related to overall survival and disease-free survival of patients. As an example, low expression of miR-125b is associated with poor prognosis in patients with ovarian cancer, while high expression of miR-222 is associated with disease recurrence [34].
On the therapeutic side, changes in miRNA expression can be used as an indicator of treatment response. As an example, miR-34a expression levels are significantly elevated in patients who respond to chemotherapy, which may help predict patient sensitivity to specific treatment regimens [35]. In addition, miRNAs can also be used as therapeutic targets to intervene in the development of ovarian cancer by regulating their expression levels. For example, exogenous administration of miR-200c mimetic can enhance the sensitivity of ovarian cancer cells to chemotherapeutic agents [36].
Although miRNAs have made significant progress as biomarkers for ovarian cancer, there are still some challenges. First, the detection methods and standards of miRNA in different studies are different, which leads to inconsistent results. Second, the stability and extraction efficiency of miRNAs may vary across different sample types, which may affect their reliability as biomarkers. In addition, the biological functions and mechanisms of action of miRNAs still need to be further elucidated in order to better understand and utilize their role in disease.
Future research needs to focus on the development of standardized miRNA assays, the establishment of large, multicenter clinical cohorts, and in-depth exploration of the specific mechanisms of action of miRNAs in ovarian cancer. Through these efforts, miRNAs are expected to become indispensable biomarkers for early diagnosis, prognosis assessment, and personalized treatment of ovarian cancer.
conclusion
The importance of miRNA as a biomarker for the early detection of ovarian cancer has been confirmed in several studies. They are not only involved in the development of ovarian cancer, but also show great potential in disease surveillance and treatment. Despite the challenges, miRNA testing is expected to play a more critical role in the clinical management of ovarian cancer with the advancement of technology and in-depth research. Future efforts should focus on standardizing testing processes, reducing costs, and improving the clinical applicability of testing to better serve patients and practice.
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