Serum miRNA‑204‑5p as a potential non‑invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping

Abstract

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results

“…This miRNA is down-regulated in endometriosis [70] and targets SP1, a transcription factor involved in the pathogenesis of endometriosis and estrogen metabolism [71]. Finally, miRNA-204-5p was up-regulated in the OCP group; it promotes apoptosis by targeting BCL2 in prostate cells [72] and is a tumor suppressor in breast cancer [73], and lower levels predict lymph node negative status in endometrial cancers [74].…”

MicroRNAs as Potential Biomarkers in Gynecological Cancers

“…The prognostic factor considered critical in patients are lymph nodes, which are the first spread place of cancer cells. Metastasis to pelvic lymph nodes is related to the stage of cancer development [ 94 , 95 , 96 , 97 ]. Routine lymphadenectomy is being replaced by sentinel lymph node mapping.…”

“…Downregulation of miR-204-5p was associated with lymph node metastasis. This molecule has turned out to be an excellent biomarker for the assessment of lymph nodes along with their mapping [ 94 ].…”

The Role of miRNAs in the Development, Proliferation, and Progression of Endometrial Cancer

“…The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method for total lymphadenectomy in the EC [125]. However, controversy remains over the use of SLNM in high-risk diseases and its false-negative rate (3%) [126]. Reliable SLNM mapping requires surgeons and institutions to be equipped with appropriate knowledge and skills.…”

“…Table 3 summarizes the above data. [128] miR-107-5p [68] miR-429 [129,130] miR-501 [131] miR-576-5p [132] Downregulation miR-24b-5p [133] miR-26a-5p [82] miR-34a [65,66] miR-34b-5p [134] miR-34c-3p [134] miR-34c-5p [134] miR-148b [71] miR-204-5p [126] miR-505 [135] 2.2.5. The Impact of miRNA Changes on Survival and Recurrence in Patients with Endometrial Cancer Mortality related to endometrial cancer continues to increase [136].…”