Background
Among all gynecological malignancies, ovarian cancer (OC) is prone to recurrence, metastasis, and resistance, and has the highest mortality rate. Furthermore, China is about to face the risk of increased incidence of the disease. This study aimed to identify potential novel tumorigenesis and prognostic genes in OC.
Conclusions
The study provided a novel view on the biological significance and function of NOTCH2NLA and confirmed that NOTCH2NLA plays a significant role in OC prognosis by affecting EMT, which could be used as a new biomarker for OC prognosis.
Methods
The Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) project were used to obtain mRNA sequencing datasets and clinical information to identify candidate genes critical to OC carcinogenesis and progression. The potential genes affecting OC were performed by comprehensive survival analysis, followed by external validation. Cell proliferation, wound healing, and transwell assays validated the effects of a potential gene on proliferation, migration, and invasion in the A2780 cell line. Observe xenograft formation in nude mice and use immunohistochemistry to determine the expression of epithelial-mesenchymal transition (EMT)-related proteins in xenograft tumors after gene silencing. Two-tailed Student's t-tests were used for two-group comparisons in in vivo and in vitro experiments.
Results
The current study developed an eight-gene model for predicting the survival of patients with OC, in which PI3, CCDC80, IL27RA, HERC1, and NOTCH2NLA represented adverse, HMGB3, CXCL11, and CXCL9 represented protective prognosis. Further, repression of NOTCH2NLA, the selected potential gene, blocked the proliferation, migration, and invasion of A2780 cells in vitro and inhibited the growth of xenograft tumors in vivo. Finally, we revealed that the expression of NOTCH2NLA in OC negatively correlated with that of E-cadherin and positively correlated with that of vimentin and SNAI2. Conclusions: The study provided a novel view on the biological significance and function of NOTCH2NLA and confirmed that NOTCH2NLA plays a significant role in OC prognosis by affecting EMT, which could be used as a new biomarker for OC prognosis.