KAISO Promotes Poor Prognosis in Hepatocellular Carcinoma Patients by Enhancing Neutrophil Infiltration via IGFBP1

Abstract

Background KAISO is a transcriptional regulator involved in gene expression, cell proliferation, and apoptosis, linked to cancer prognosis and tumor aggressiveness, making it a potential bi-omarker and therapeutic target. Methods: We used bioinformatics analyses to evaluate KAISO expression and its effect on survival prognosis across 33 types of pan-cancer. We also examined the link between KAISO expression and immune cell infiltration. To investigate the control of down-stream proteins by KAISO, we used dual-luciferase reporter assays, electrophoretic mobility shift assays (EMSA), and chromatin immunoprecipitation (ChIP). Additionally, we validated the role of KAISO in regulating immune cell infiltration using a subcutaneous tumor model in animals and human tumor samples. Results: Our research revealed that KAISO is crucial in regulating the growth and progression of various malignancies, including hepatocellular carcinoma (HCC). We demonstrated that high KAISO expression is associated with poor prognosis in HCC. KAISO was found to regulate the transcription of IGFBP1 and neutrophil infiltration and influence HCC pro-liferation through cell cycle-related molecular pathways. Finally, we confirmed that reducing KAISO expression can inhibit neutrophil infiltration and tumor growth. Conclusion: Our findings suggest that KAISO could be an important biomarker and molecular target for HCC patients.