Abstract
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.