Shi Chuanbing, Sha Ling, Zhang Zhe, Gu Xuefeng
Department of Pathology, Nanjing Pukou People's Hospital, Nanjing, Jiangsu, China.
Department of Neurology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
Medicine (Baltimore). 2025 May 16;104(20):e42483. doi: 10.1097/MD.0000000000042483.
N-Myc downstream-regulated gene 3 (NDRG3), a member of the NDRG family, plays an important role in the development, progression, invasiveness, and metastasis of multiple tumor types. This study focuses on NDRG3 expression in epithelial ovarian cancer (EOC) and the correlation between NDRG3 expression and prognostic indicators. First, the LinkedOmics database was used to analyze the expression of genes associated with NDRG3, and then gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses and methylation analysis of NDRG3-related genes were performed to identify co-expressed genes. A protein-protein interaction network was constructed using the STRING database. Subsequently, quantitative polymerase chain reaction was performed to determine the mRNA expression level of NDRG3 in 22 fresh EOC tissue samples. In addition, immunohistochemistry was performed to detect the expression of NDRG3 protein in 110 EOC microarray samples. Cox regression and Kaplan-Meier survival analyses were performed to assess the prognostic value of NDRG3. Bioinformatics analysis showed that NDRG3 had a broad impact on the transcriptome and that genes that were co-expressed with NDRG3 were primarily involved in organ- or tissue-specific immune response, response to chemokine, interleukin-1 production, and other related pathways. The KEGG pathway analysis suggested that genes co-expressed with NDRG3 were also enriched in signaling pathways, including the interleukin-17 signaling pathway. The mRNA expression levels of NDRG3 were significantly higher in EOC tissues than in paracancerous nontumor tissues (P < .01). NDRG3 expression in EOC was correlated with distant metastasis (P = .02), tumor-node-metastasis stage (P = .03), and patient prognosis (P = .01). Moreover, the disease-free survival and overall survival times of EOC patients decreased with increasing NDRG3 expression. High NDRG3 expression and lymph node metastasis were identified as independent prognostic factors in 110 EOC patients. NDRG3 plays a key role in ovarian cancer progression. High NDRG3 expression is correlated with multiple clinicopathologic features of EOC and may be an indicator of a poor prognosis in EOC.
N-Myc下游调控基因3（NDRG3）是NDRG家族的成员之一，在多种肿瘤类型的发生、发展、侵袭和转移过程中发挥着重要作用。本研究聚焦于NDRG3在上皮性卵巢癌（EOC）中的表达以及NDRG3表达与预后指标之间的相关性。首先，利用LinkedOmics数据库分析与NDRG3相关的基因表达情况，然后进行基因本体论和京都基因与基因组百科全书（KEGG）功能富集分析以及NDRG3相关基因的甲基化分析，以确定共表达基因。使用STRING数据库构建蛋白质-蛋白质相互作用网络。随后，进行定量聚合酶链反应以测定22例新鲜EOC组织样本中NDRG3的mRNA表达水平。此外，采用免疫组织化学方法检测110例EOC芯片样本中NDRG3蛋白的表达情况。进行Cox回归分析和Kaplan-Meier生存分析以评估NDRG3的预后价值。生物信息学分析表明，NDRG3对转录组有广泛影响，与NDRG3共表达的基因主要参与器官或组织特异性免疫反应、对趋化因子的反应、白细胞介素-1的产生以及其他相关途径。KEGG通路分析表明，与NDRG3共表达的基因也富集于信号通路，包括白细胞介素-17信号通路。EOC组织中NDRG3的mRNA表达水平显著高于癌旁非肿瘤组织（P < 0.01）。EOC中NDRG3的表达与远处转移（P = 0.02）、肿瘤-淋巴结-转移分期（P = 0.03）和患者预后（P = 0.01）相关。此外，EOC患者的无病生存期和总生存期随着NDRG3表达的增加而缩短。在110例EOC患者中，高NDRG3表达和淋巴结转移被确定为独立的预后因素。NDRG3在卵巢癌进展中起关键作用。高NDRG3表达与EOC的多种临床病理特征相关，可能是EOC预后不良的一个指标。
