Single-Cell RNA-Sequencing Portraying Functional Diversity and Clinical Implications of IFI6 in Ovarian Cancer

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies. Most patients die of metastasis due to a lack of other treatments aimed at improving the prognosis of OC patients. In the present study, we use multiple methods to identify prognostic S1 as the dominant subtype in OC, possessing the most ligand-receptor pairs with other cell types. Based on markers of S1, the consensus clustering algorithm is used to explore the clinical treatment subtype in OC. As a result, we identify two clusters associated with distinct survival and drug response. Notably, IFI6 contributes to the cluster classification and seems to be a vital gene in OC carcinogenesis. Functional enrichment analysis demonstrates that its functions involve G2M and cisplatin resistance, and downregulation of IFI6 suppresses proliferation capabilities and significantly potentiates cisplatin-induced apoptosis of OC cells in vitro. To explore possible mechanisms of IFI6 influencing OC proliferation and cisplatin resistance, GSEA is conducted and shows that IFI6 is positively correlated with the NF-kappa B pathway, which is validated by RT-qPCR. Significantly, we develop a prognostic model including IFI6, RiskScore, which is an independent prognostic factor and presents encouraging prognostic values. Our findings provide novel insights into elucidating the biology of OC based on single-cell RNA-sequencing. Moreover, this approach is potentially helpful for personalized anti-cancer strategies and predicting outcomes in the setting of OC.

Automated summary

In this study, prognostic subtype S1 was identified as dominant in ovarian cancer (OC) and associated with distinct survival and drug response clusters. IFI6, a vital gene in OC carcinogenesis, was found to suppress proliferation capabilities and enhance cisplatin-induced apoptosis. Functional enrichment analysis revealed a correlation between IFI6 and the NF-kappa B pathway, validating its role in OC biology. The development of a prognostic model incorporating IFI6, RiskScore, provides promising prognostic values and potential for personalized anti-cancer strategies in OC management.