Identification of differentially expressed miRNAs in early-stage cervical cancer with lymph node metastasis across The Cancer Genome Atlas datasets

利用癌症基因组图谱数据集鉴定早期宫颈癌伴淋巴结转移中差异表达的miRNA

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Abstract

BACKGROUND AND AIM: Previous studies have suggested that lymph node metastasis (LNM) in early-stage cervical cancer (CESC) may affect the prognosis of patients and the outcomes of subsequent adjuvant therapy. However, research focused on miRNA expression in early-stage CESC patients with LNM remains limited. Therefore, it is necessary to identify prognostic miRNAs and determine their molecular mechanisms. METHODS: We evaluated the differentially expressed genes in early-stage CESC patients with LNM compared to patients without LNM and evaluated the prognostic significance of these differentially expressed genes by analyzing a public dataset from The Cancer Genome Atlas. Potential molecular mechanisms were investigated by gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. RESULTS: According to the The Cancer Genome Atlas data, hsa-miR-508, hsa-miR-509-2, and hsa-miR-526b expression levels were significantly lower in early-stage CESC patients with LNM than in patients without LNM. A multivariate analysis suggested that three miRNAs were prognostic factors for CESC (P<0.05). The target genes were identified to be involved in the MAPK, cAMP, PI3K/Akt, mTOR, and estrogen cancer signaling pathways. Protein-protein interaction network analysis showed that TP53, MMP1, NOTCH1, SMAD4, and NFKB1 were the most significant hub proteins. CONCLUSION: Our results indicate that hsa-miR-508, hsa-miR-509-2, and hsa-miR-526b may be potential diagnostic biomarkers for early-stage CESC with LNM, and serve as prognostic predictors for patients with CESC.

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