Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer

Ovarian cancer (OC) often presents at an advanced stage and is still one of the most frequent causes of gynecological cancer-related mortality worldwide. The nuclear factor erythroid-2 (NFE2) transcription factors include nuclear factor, erythroid 2 like 1 (NFE2L1), NFE2L2, and NFE2L3. NFE2 members bind to the antioxidant-response element (ARE) region and activate the expression of targeted genes. The distinct functions of NFE2 members in OC remain poorly elucidated. Several online bioinformatics databases were applied to determine gene expression, prognosis, mutations, and immune infiltration correlation in OC patients. NFE2L1 and NFE2L2 were decreased in OC, whereas NFE2L3 was increased. NFE2L2 and NFE2L3 were significantly correlated with the clinical stages of OC. High NFE2L1 level was significantly associated with short progression-free survival (PFS) in patients with OC (HR = 1.18, P = 0.021), while high NFE2L2 expression strongly correlated with long PFS (HR = 0.77, P = 0.00067). High NFE2L3 expression was associated with better overall survival and postprogression survival in OC. Functional analysis showed that NFE2 members mainly focused on transcription coactivator activities. Genetic alterations of NFE2 members were found in 13% of OC patients, and amplification ranked the top. The expression of NFE2 members was significantly correlated with immune infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in OC. Our study provides novel insights into the roles and prognostic potential of NFE2 family members in OC.