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

血清 miRNA-204-5p 作为使用哨兵淋巴结定位诊断子宫内膜癌的潜在非侵入性生物标志物

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作者:Cailiang Wu, Xuexin Zhou, Jiayong Li, Ruiying Xiao, Haomin Xin, Lei Dai, Yaping Zhu, Wei Bao

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.

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