SLNM was first reported in lymphangiogram of penile carcinoma in 1977 [15]. Nowadays, SLNM has been applied in many malignancies, instead of lymphadenectomy, including the breast cancer and vulva cancer, and first applied in EC in 1996 [16]. Tracer injected in corpus uterus or cervix, which flowing along lymphatic channels, and accumulates in the first station, the so-called SLN, recognized as the first site of extra-uterus metastases [8]. Though the technology showed advantages throughout the treatment with similar survival but less surgical complications compared to systematic lymphonodectomy. Some drawbacks should not be ignored. Such as, the accuracy of intraoperative frozen section, researches figured that 46.58%-76.92% SLN positive cervical cancer patients were missed during the frozen section [17, 18]. Besides, on one hand, the rate of successful mapping range from 23% to 100%, and the difference may be influenced by the experience of surgeons [19]. On the other hand, there are 16% EC patients suffered para-aortic area metastases with pelvic nodes negative [20]. Additionally, for the tracer selection, the signal of blue dyes influenced by the adipose, while the technetium 99 and tricarbocyanine dye require complex imaging equipment, and the technologies are difficult to be popularized [21].
Early in 2014, researchers used CK19 mRNA at 250 copies from lymph node tissue during the operation to predict the metastases with sensitivity of 82.4%, specificity of 99.2%, however this method was also based on the dissection of lymph node during the surgery [22]. MicroRNAs as non-protein coding RNAs are associated with post-transcriptional regulation, and play roles in many cellular processes, and induced the cancer development. Previous studies also found that effective diagnostic value of microRNAs in cancers, Shimomura and colleagues figured that preoperative combination of serum miR-1246, miR-1307-3p, miR-4634, miR-6861-5p and miR-6875-5p detected the early breast cancer with a sensitivity of 97.3%, specificity of 82.9% [11]. The serum of miR-135a distinguished non-small cell lung cancer from healthy with specificity and sensitivity of 83.1% and 81.3% respectively [23]. Researchers also found that lower expression of serum miR-204 predicted worse survival in gastric cancer patients [24].The current study has found serum miR-204-5p was a more convenient method pre-operation to predict the status of lymph node metastases combined with SLNM in treatment of EC patients, with a sensitivity of 87.2%, a specificity of 80.0% (AUC=0.923, 95%CI[0.847, 1.000], p=0.002).
MiR-204 regulated adipogenesis by inhibiting the activation of Wnt/β-catenin signaling pathway and reduced insulin production by downregulating insulin transcription factor-MAFA [25, 26]. Abnormal expression of miR-204 was found in kinds of cancer. Zanette and colleagues found that miR-204 over expression in acute lymphocytic leukemia [27]. While the level of miR-204 was significant lower than normal tissue, and was negative associated with lymph node metastases in gastric cancer and bladder cancer [28, 29], which consistence with our previous study, the expression of miR-204-5p was down-regulation in EC tissue compared to normal tissue, and even lower in the positive lymph nodes [12]. Moreover, recent evidence figured out that the serum levels of miR-204-5p in gastric cancer patients were lower than benign patients, and pointed out that miR-204-5p targeted at CXCR4 and CXCL12 to suppress the lymph node metastases [30]. In accordance with the serum miR-204-5p level, we demonstrated that lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues. Therefore, serum miR-204-5p may be an efficient biomarker in EC patients for detecting the status of lymph node metastases pre-operation, with little cost and more convenient.
There were some limitations in our study. Firstly, the samples included in this research was small, and the sentinel lymph node positive case was only five; Secondly, we didn’t explore the prognostic value of serum miR-204-5p in EC patients. In the further research, we will enlarge the size of study, and try to find the cut-off of serum miR-204-5p in lymph node metastatic EC patients.
In conclusion, our data demonstrated that the serum miR-204-5p was lower in positive SLN than negative SLN, and serum miR-204-5p may be an efficient biomarker in predicting the lymph node metastases pre-operation. Thus may be helpful for clinical decision making for lymphonodectomy or sentinel lymph node mapping in EC patients.