Correlation Between High Expression of FOXA2 and Improved Overall Survival in Ovarian Cancer Patients

BACKGROUND: The aim of the present work was to evaluate FOXA2 expression in ovarian cancer and to use integrated bioinformatics analysis to correlate it with patient prognosis. MATERIAL/METHODS: FOXA2 expression was evaluated in multiple cancers in The Cancer Genome Atlas database. A protein–protein interaction (PPI) network relevant to FOXA2 was constructed using the Search Tool for Retrieval of Interacting Genes/Proteins (STRIN). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed of FOXA2 and relevant genes. Correlations between overall survival (OS), disease-free survival, and FOXA2 expression were evaluated. An immunohistochemical assay (IHC) was used to test for FOXA2 protein expression in 79 ovarian cancer specimens. RESULTS: FOXA2 mRNA was upregulated in colorectal, stomach, liver, and endometrial cancers. In the PPI network, 21 protein nodes and 533 edges were constructed with a local clustering coefficient of 0.698, which indicated significant PPI enrichment (P<0.01). FOXA2 and relevant genes were mainly enriched in the signaling pathways regulating pluripotency of stem cells, cancer, and AMPK. A survival analysis indicated that OS was significantly longer in patients with higher versus lower FOXA2 protein expression (HR=0.73, P<0.01). The IHC assay showed that the FOXA2 protein was mainly positively expressed in the nucleoplasm of tumor cells with brown-yellow staining. Of the 79 ovarian cancer samples, 31 (39.2%) highly expressed FOXA2. The FOXA2 gene was correlated with International Federation of Gynecology and Obstetrics staging and with lymph node metastasis (both P<0.05). CONCLUSIONS: Upregulation of the FOXA2 gene was correlated with improved OS in patients with ovarian cancer and it can be used as a prognostic biomarker and potential treatment target.