IKBIP as a prognostic biomarker and immunotherapeutic target regulates JAK-STAT3 signaling pathway to promote cervical cancer

Background Cervical cancer (CC) represents a significant threat to women's health globally. Although IKBIP has been recognized as an oncogene, although little is known about how it contributes to cancer, and it has predominantly been associated with driving malignant progression in gliomas. Further investigation into the function of IKBIP in other cancer types, including CC, is essential to fully understand its potential implications for tumorigenesis and progression in various malignancies. Methods IKBIP expression was analyzed in CC tissues using the GEPIA and GEO databases. The transcriptomic data and clinical characteristics of 306 patients with CC were obtained from TCGA, and clustering was performed using X-tile software. Additionally, to validate the prognostic significance of IKBIP, protein levels in normal and cancerous tissues were compared through IHC. The TIDE score was employed as an indicator of the response to immunotherapy. Furthermore, our research sought to investigate any possible connectionsbetween IKBIP and immunological genes, as well as their influence on the development of TMB and drug sensitivity. The impact of IKBIP on CC cells' capacity for invasion, migration, and proliferation were investigated using CCK-8, EdU, and transwell assays. To clarify IKBIP's function in controlling the JAK-STAT signaling cascade and its contribution to the progression of CC, we utilized the JAK-STAT pathway agonist Colivelin in rescue experiments. The influence of IKBIP on CC development was also validated in a xenograft tumor model. Results Our research showed that the tissues of cervical cancer overexpress IKBIP, which could be a potential oncogene associated with cervical cancer. According to nomogram creation, ROC curve analysis, and Kaplan-Meier survival analysis, IKBIP may be a biomarker for a bad prognosis in CC. Furthermore, the expression of IKBIP exhibited a strong correlation with immune infiltration, TMB and drug sensitivity in CC. In vitro experiments indicated that IKBIP functions as an oncogene, because inhibiting its expression dramatically reduced cervical cancer cells' capacity to proliferate, migrate, and invade using the CCK8, EdU, and transwell tests, respectively. Additionally, our findings suggest that IKBIP may promote cervical cancer progression by regulating the JAK-STAT signaling pathway. Rescue experiments demonstrated that the JAK-STAT pathway activator, Colivelin, could mitigate the inhibitory effects of IKBIP knockdown on cervical cancer cell behavior. We successfully constructed the cervical cancer xenograft mouse model and in vivo experiments demonstrated that the expression of IKBIP is closely correlated with the malignancy of cervical cancer, and also provided more evidence that IKBIP contributes to the advancement of cervical cancer. Conclusion In summary, this study offers novel insights for CC by establishing IKBIP as a robust prognostic indicator. Our findings suggest that IKBIP not only correlates with adverse clinical outcomes but also influences tumor immunogenicity and response to treatment. Furthermore, IKBIP is significantly correlated with the progression of CC mediated by the JAK/STAT3 signaling pathway, and it may become an effective therapeutic target.