Cervical cancer (CC) is a significant global health threat for women worldwide. Although IKBIP has been recognized as an oncogene, little is known about its contribution to CC. Therefore, we aimed to analyze IKBIP expression, its correlation with clinicopathological parameters, and its association with the prognosis in CC. IKBIP expression in CC tissues was analyzed using the Gene Expression Profiling Interactive Analysis and Gene Expression Omnibus databases. The transcriptomic data and clinical characteristics of 306 patients with CC were obtained from the Cancer Genome Atlas, and clustering was performed using the X-tile software. Additionally, to validate the prognostic significance of IKBIP, protein levels in normal and cancerous tissues were compared by immunohistochemistry. The Tumor Immune Dysfunction and Exclusion score was used as an indicator of potential response to immunotherapy. Furthermore, we investigated the possible connections between IKBIP and immunological genes and their influence on the development of tumor mutation burden (TMB) and drug sensitivity. The impact of IKBIP on CC cell proliferation, invasion, and migration was investigated using CCK-8, EdU, and transwell assays. To clarify the role of IKBIP in controlling the JAK-STAT signaling cascade and its contribution to the progression of CC, we used the JAK-STAT pathway agonist colivelin in rescue experiments. The effect of IKBIP on CC development was validated using a xenograft tumor model. Our study showed that IKBIP is overexpressed in CC tissues, suggesting that it may be an oncogene associated with CC. Based on nomogram creation, receiver operating characteristic curve analysis, and Kaplan–Meier survival analysis, IKBIP was found to be a biomarker for poor prognosis in CC. Furthermore, IKBIP expression was strongly correlated 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 the capacity of CC cells to proliferate, migrate, and invade, as indicated using the CCK8, EdU, and transwell assays. Additionally, our findings suggested that IKBIP promotes CC progression by regulating the JAK-STAT signaling pathway. Rescue experiments demonstrated that the JAK-STAT pathway activator colivelin mitigated the inhibitory effects of IKBIP knockdown on CC cell behavior. We successfully constructed a CC xenograft mouse model, and in vivo experiments demonstrated that the expression of IKBIP is closely correlated with the malignancy of CC, providing further evidence that IKBIP contributes to the advancement of CC. This study offers novel insights into CC by establishing IKBIP as a robust prognostic marker. Our findings suggest that IKBIP not only correlates with adverse clinical outcomes but also influences tumor immunogenicity and treatment response. Furthermore, IKBIP was significantly correlated with CC progression mediated by the JAK/STAT3 signaling pathway and may be an effective therapeutic target.
Wang et al. (Fri,) studied this question.