miR-141-3p/ZEB1轴在子宫内膜癌组织的表达水平和临床价值

Expression Levels and Clinical Value of the miR-141-3p/ZEB1 Axis in Endometrial Cancer Tissues

    摘要
  • 摘要:
    目的 筛选子宫内膜癌（EC）关键miRNA-mRNA轴，探讨miR-141-3p/ZEB1轴在EC中的临床意义及其中医微观辨证价值。
    方法 整合TCGA、GEO、dbDEMC等多数据库筛选EC差异表达miRNA-mRNA轴，采用qRT-PCR法检测66例EC组织及配对癌旁正常组织中候选miRNAs及mRNAs的表达水平。基于TCGA数据集分析miR-141-3p/ZEB1表达模式与患者预后的相关性。收集EC患者的临床样本及中医证型资料，比较不同中医证型间miR-141-3p/ZEB1的表达差异，采用Spearman相关性分析、多因素Logistic回归、受试者工作特征（ROC）曲线及决策曲线分析，系统评估该分子对中医证型的鉴别效能与微观辨证价值。
    结果 miR-141-3p/ZEB1为EC关键负向调控轴，肿瘤组织中miR-141-3p显著高表达（P<0.01），ZEB1显著低表达（P<0.05），二者表达呈显著负相关（r=-0.482，P<0.001）；miR-141-3p高表达/ZEB1低表达模式与患者不良预后密切相关。中医证型分析显示，miR-141-3p在湿热瘀毒证中表达最高，肝肾阴虚证中最低（P<0.05）。miR-141-3p水平升高与湿热瘀毒证风险增加（OR=2.64，95%CI：1.39~5.04，P=0.003）及肝肾阴虚证风险降低（OR=0.40，95%CI：0.18~0.91，P=0.029）显著相关。其鉴别2种证型的曲线下面积（AUC）分别为0.833、0.873，鉴别湿热瘀毒证的临床净获益达0.242 4。
    结论 miR-141-3p/ZEB1是EC关键调控轴，可作为该病预后评估的潜在生物标志物；miR-141-3p是中医证型的独立相关因素，提示其具有潜在微观辨证价值，为EC的中西医结合精准诊疗提供依据。

     

    Abstract:
    OBJECTIVE To screen key miRNA-mRNA axes in endometrial cancer (EC) and explore the clinical significance and TCM micro-differentiation value of the miR-141-3p/ZEB1 axis in EC.
    METHODS Differentially expressed miRNA-mRNA axes in EC were screened by integrating multiple databases such as TCGA, GEO, and dbDEMC. The expression levels of candidate miRNAs and mRNAs in 66 EC tissues and paired adjacent normal tissues were detected by qRT-PCR. The correlation between miR-141-3p/ZEB1 expression patterns and patient prognosis was analyzed based on the TCGA dataset. Clinical samples and TCM syndrome data of EC patients were collected, and the expression differences of miR-141-3p/ZEB1 among different TCM syndromes were compared. Spearman correlation analysis, multinomial logistic regression, receiver operating characteristic (ROC) curve analysis, and decision curve analysis were used to systematically evaluate the differential efficacy and micro-differentiation value of this molecule in TCM syndrome differentiation.
    RESULTS miR-141-3p/ZEB1 was identified as the key negative regulatory pair in EC. miR-141-3p was significantly upregulated (P<0.01) while ZEB1 was significantly downregulated (P<0.05) in cancer tissues, with a significant negative correlation between their expressions (r=-0.482, P<0.001). The pattern of high miR-141-3p expression/low ZEB1 expression was closely associated with poor prognosis of patients. TCM syndrome analysis showed that miR-141-3p expression was the highest in Damp-Heat Toxin Stagnation syndrome and the lowest in Liver-Kidney Yin Deficiency syndrome (P<0.05). Elevated miR-141-3p levels were significantly associated with an increased risk of Damp-Heat Toxin Stagnation syndrome (OR=2.64, 95%CI: 1.39–5.04, P=0.003) and a decreased risk of Liver-Kidney Yin Deficiency syndrome (OR=0.40, 95%CI: 0.18–0.91, P=0.029). The AUCs for identifying the two syndromes were 0.833 and 0.873 respectively, and the clinical net benefit for identifying Damp-Heat Toxin Stagnation syndrome reached 0.242 4.
    CONCLUSION miR-141-3p/ZEB1 is a key regulatory axis for EC and can serve as a potential biomarker for prognostic assessment of the disease. miR-141-3p is an independent correlation factor for TCM syndrome types, suggesting its potential micro-differentiation value and providing a basis for the integrated TCM and Western medicine precision diagnosis and treatment of EC.

     

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