Background: Activation of the NOTCH signaling pathway is
associated with tumorigenesis. The aim of this study was to investigate
NOTCH pathway gene functions and regulatory mechanisms in ovarian cancer
(OC). Methods: We conducted a bioinformatics analysis of publicly
available datasets in order to identify potential NOTCH-related
mechanisms, associated genes, biological pathways, and their relation to immune
function. Results: Significant differential expression of the
NOTCH pathway genes DLL1, DLL3, DLL4,
HES1, HEY1, JAG1, NOTCH2, NOTCH3,
and NOTCH4 was observed between OC samples and normal controls. Low
expression of DLL4 and of NOTCH4 in OC patients was associated with
International Federation of Gynecology and Obstetrics (FIGO) stage (p 0.001 and p = 0.036, respectively), while high expression of
NOTCH3 was associated with race (p = 0.039) and age (p = 0.044). JAG2 and NOTCH1 expression were significantly associated with
progression-free interval (PFI) (p = 0.011 and p = 0.039,
respectively). DLL1 (Hazard Ratio (HR): 2.096; 95% CI: 1.522–2.886,
p 0.001) and NOTCH1 (HR: 0.711; 95% CI: 0.514–0.983,
p = 0.039) expression were independently associated with PFI in
multivariate analysis. DLL1, DLL3, JAG1,
JAG2, NOTCH3 and NOTCH4 expression could significantly
differentiate OC from non-cancer samples. Genes associated with the
NOTCH pathway were mainly enriched in five signaling pathways: the
NOTCH signaling pathway, breast cancer, endocrine resistance, Th1 and
Th2 cell differentiation, and oxidative phosphorylation. The expression of
NOTCH pathway genes was significantly associated with immune cell
infiltration. Conclusions: NOTCH pathway genes appear to play
an important role in the progression of OC by regulating immune cells, endocrine
resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation.
JAG2 and NOTCH1 are potential biomarkers and therapeutic
targets for the treatment of OC.