章伟玲,王微微,孙琰珺,等.尿微小RNA特征谱预测宫颈癌淋巴结转移[J].肿瘤学杂志,2025,31(11):930-937.
尿微小RNA特征谱预测宫颈癌淋巴结转移
Urinary MicroRNA Signature for Predicting Lymph Node Metastasis in Cervical Cancer
投稿时间:2024-12-25  
DOI:10.11735/j.issn.1671-170X.2025.11.B002
中文关键词:  宫颈肿瘤  淋巴结转移  尿液样本  微小RNA
英文关键词:cervical neoplasms  lymph node metastasis  urine sample  microRNA
基金项目:江苏省卫生健康委面上项目(M2020010)
作者单位
章伟玲 南通市肿瘤医院南通大学附属肿瘤医院 
王微微 南通市肿瘤医院南通大学附属肿瘤医院 
孙琰珺 南通市肿瘤医院南通大学附属肿瘤医院 
姚 涓 南通市肿瘤医院南通大学附属肿瘤医院 
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中文摘要:
      摘 要:[目的] 筛选宫颈癌患者淋巴结转移(lymph node metastasis ,LNM)阳性相关的尿微小RNA(microRNA,miRNA),并评价其诊断价值。[方法] 收集2017年1月至12月在南通市肿瘤医院诊治的宫颈癌患者术前尿液样本(发现集),包括12例LNM阳性患者和13例LNM阴性患者,使用GeneChip miRNA 3.0阵列鉴定尿液全基因组miRNA谱。收集2018年1月至2023年11月96例宫颈癌患者的尿液样本(验证集),采用逆转录实时定量聚合酶链式反应法检测尿miRNA表达,并使用受试者工作特征曲线和Logistic回归分析来确定与LNM阳性相关的miRNA,并构建预测模型。[结果] 微阵列表达谱鉴定了33个差异表达的miRNA,进一步缩窄筛选标准(错误发现率<0.05,倍数变化<0.05或>2.0),共鉴定8种miRNA差异表达:miR-7a-5p、miR-483-5p、miR-552和miR-92b-5p过表达;miR-375、miR-486-5p、miR-92a-3p和miR-195-3p低表达。经验证集验证,miR-483-5p(2.64 vs 1.78,P=0.008)、miR-552(2.63 vs 1.59,P=0.001)、miR-92b-5p(2.60 vs 1.85,P=0.019)在LNM阳性组中表达上调;miR-375(1.35 vs 2.19,P<0.001)、miR-486-5p(1.57 vs 2.26,P=0.003)在LNM阳性组中表达下调。多因素分析显示尿miRNA(miR-483-5p、miR-552、miR-92b-5p、miR-375)与LNM阳性状态存在独立的相关关系(P<0.05)。构建这4种miRNA组合模型,该模型正确地分类了78.57%(11/14)的LNM阳性样本和93.90%(77/82)的LNM阴性样本。[结论] 一种包含miR-483-5p、miR-552、miR-92b-5p和miR-375的尿液 miRNA 特征有望成为预测宫颈癌淋巴结转移的无创生物标志物。
英文摘要:
      Abstract:[Objective] To identify urinary microRNA (miRNA) signatures associated with lymph node metastasis (LNM) in cervical cancer and assess their diagnostic potential. [Methods] Preope-rative urine samples were collected from cervical cancer patients who underwent radical hysterectomy and pelvic lymphadenectomy at Nantong Tumor Hospital between January and December 2017. A discovery set (12 positive LNM and 13 negative LNM patients) was analyzed using GeneChip miRNA 3.0 arrays to define genome-wide miRNA profiles. From January 2018 to November 2023, urine samples from 96 patients with cervical cancer were collected (validation set), differentially expressed miRNAs were validated by real-time quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic curves and Logistic regression analy-ses were employed to evaluate diagnostic performance and construct a predictive model. [Results] Microarray analysis identified 33 differentially expressed miRNAs. Applying stricter criteria (false discovery rate <0.05, fold change <0.05 or >2.0), eight miRNAs were identified as differentially expressed: miR-7a-5p, miR-483-5p, miR-552 and miR-92b-5p were upregulated; miR-375, miR-486-5p, miR-92a-3p and miR-195-3p were downregulated. In the validation set, miR-483-5p (2.64 vs 1.78,P=0.008), miR-552(2.63 vs 1.59,P=0.001), and miR-92b-5p (2.60 vs 1.85,P=0.019) were significantly upregulated, whereas miR-375 (1.35 vs 2.19,P<0.001) and miR-486-5p (1.57 vs 2.26,P=0.003) were downregulated in positive LNM patients (all P<0.05). Multivariate analysis confirmed that miR-483-5p, miR-552, miR-92b-5p, and miR-375 were independently associated with positive LNM status. A combination model based on these four miRNAs correctly classified 78.57% (11/14) of positive LNM and 93.90% (77/82) of negative LNM samples. [Conclusion] A urinary miRNA signature comprising miR-483-5p, miR-552, miR-92b-5p and miR-375 shows promise as a noninvasive biomarker for predicting LNM in cervical cancer.
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