Chen Qian, Zeng Xiaoyun, Huang Dongping, Qiu Xiaoqiang
Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China,
Cancer Manag Res. 2018 Nov 28;10:6489-6504. doi: 10.2147/CMAR.S183488. eCollection 2018.
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.
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.
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 (<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.
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.
既往研究表明,早期宫颈癌(CESC)中的淋巴结转移(LNM)可能影响患者预后及后续辅助治疗的效果。然而,针对伴有LNM的早期CESC患者中miRNA表达的研究仍然有限。因此,有必要鉴定预后相关的miRNA并确定其分子机制。
我们评估了伴有LNM的早期CESC患者与无LNM患者之间的差异表达基因,并通过分析来自癌症基因组图谱(The Cancer Genome Atlas)的公共数据集评估这些差异表达基因的预后意义。通过基因本体论、京都基因与基因组百科全书以及蛋白质-蛋白质相互作用网络分析来研究潜在的分子机制。
根据癌症基因组图谱数据,伴有LNM的早期CESC患者中hsa-miR-508、hsa-miR-509-2和hsa-miR-526b的表达水平显著低于无LNM的患者。多变量分析表明,这三种miRNA是CESC的预后因素(<0.05)。鉴定出的靶基因参与丝裂原活化蛋白激酶(MAPK)、环磷酸腺苷(cAMP)、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)和雌激素癌症信号通路。蛋白质-蛋白质相互作用网络分析显示,TP53、基质金属蛋白酶1(MMP1)、Notch1蛋白(NOTCH1)、Smad4蛋白(SMAD4)和核因子κB1(NFKB1)是最重要的枢纽蛋白。
我们的结果表明,hsa-miR-508、hsa-miR-509-2和hsa-miR-526b可能是伴有LNM的早期CESC的潜在诊断生物标志物,并可作为CESC患者的预后预测指标。