Ovarian cancer is the sixth leading cause of mortality in women, killing more women than any other cancer of the reproductive system. A woman’s lifetime risk of developing ovarian cancer is about 1 in 78 [1]. A family history of breast or ovarian cancer is the most significant risk factor for ovarian cancer, and heritable susceptibility accounts for about 25% of all malignancies [19]. Currently, miRNAs are being investigated as serum biomarkers. These tiny non-coding RNA molecules are likely non-invasive blood biomarkers [20]. Zhang et al. reported miRNAs as diagnostic or prognostic indicators [21]. A panel of miRNAs was apparently better than traditional methods for distinguishing between malignant and reactive lesions, and among cancers with various histogenetic origins and histological subtypes of the same type of tumor. Ashrafizadeh et al. indicated that miRNAs can also function as major regulators of carcinogenesis and that targeting these molecules, or their functions, might be an effective treatment strategy [22]. Thus, our study evaluated the involvement of miR-21 in ovarian cancer progression.
We found that the expression of miR-21 was considerably elevated in sera of ovarian cancer patients compared with age-matched controls. The fold change value in serum miR-21 expression in patients with advanced stage cancer was 7.16 ± 1.57, substantially higher than for early stages, 4.46 ± 1.13. Similarly, XU et al. reported higher blood miR-21 levels in EOC patients, which correlated with FIGO stage and tumor grade [23]. Further, higher plasma miR-21 levels are linked to poor long-term prognosis. Kartika et al. found that miRNA-21 was upregulated 2.14-fold in late compared to early stages, and 6.13-fold compared to healthy controls (p 0.05) [24]. Lou et al. hypothesized that aberrant miR-21 expression affects several biological processes in ovarian cancer cells, including proliferation, migration, and invasion [25]. miR-21 appears to play a role in ovarian carcinogenesis and promotes invasion and metastasis. The precise mechanism of involvement of miRNA 21 in the progression of cancer is still unknown. Lu et al. [25] and Meng et al. [26] suggested that overexpression of miR-21 is closely linked to the negative expression of PTEN protein. Other tumor suppressor genes, such as Pdcd4, which is negatively regulated at the posttranscriptional level by miR-21, may also be involved [27, 28].
We found significant differences in miR-21 expression among serous, mucinous, and endometrioid histology, with the highest expression in the endometrioid type. Nam et al. suggested that miR-21 was the most frequently upregulated miRNA in serous ovarian carcinoma biopsies compared to normal ovarian tissue [29]. Paliwal et al. showed that RT-qPCR-calculated fold changes in miRNA-21 expression were 3.98 times higher in serous ovarian cancer compared to controls [20]. Similarly, elevated levels of 1.99- and 1.34-fold were observed for mucinous and endometrioid ovarian carcinoma, respectively. Lou et al. reported increased miRNA-21 expression in serous, mucinous, and endometrioid subtypes of EOC, but did not observe any significant differences among the three histotypes [25].
Currently, pelvic examination, transvaginal ultrasonography (TVUS), and serum CA-125 levels are standard modalities for detecting ovarian cancer. CA-125 is considered a “gold standard” tumor biomarker for this disease [30, 31]. We consistently found high serum levels in the early stages of ovarian cancer in comparison with controls and higher levels in the late stages.
We also found that sensitivity, specificity, and accuracy of miRNA-21 were superior to CA-125-96%, 88%, and 92% versus 74%, 80%, and 77%, respectively, in addition to a significant positive correlation between CA-125 and miRNA-21 among the studied groups. Consistently, Xu et al. [23] suggested that serum miR-21 could be used as a diagnostic and prognostic marker for EOC, as well as a therapeutic target. Overall, miR-21 can be used for early detection and therapy planning as a tumor biomarker for ovarian cancer.
Our study’s small sample size made it difficult to generalize the findings, which necessitated larger cohort studies. Additionally, the expense of the reagents prevented the study from involving more participants. We recommend future research into various populations, including high population sample sizes, in order to completely elucidate the role of miRNA-21 gene expression in EOC. Additional studies comparing serum miRNA-21 expression with tissue expression would unquestionably support our findings.
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