Downregulated expression of INPP4B contributes to ovarian cancer growth and immune cell infiltration

Background Ovarian cancer is the most lethal gynecological cancer worldwide. Since the early clinical symptoms are not obvious, most patients with ovarian cancer are already in an advanced clinical stage when they are diagnosed. HGSOC accounts for the greatest number of ovarian cancer deaths and shows an association between an enhanced immune response and prolonged patient survival. Methods 88 normal ovarian samples from TCGA and 149 ovarian cancer patients from GTEx were used to analyze gene expression, proteins and pathways associated with INPP4B in HGSOC, LGSOC and ovarian cancer. The correlation between INPP4B gene and immune factors was analyzed by TIMER website. The expression of INPP4B was verified by immunohistochemistry and Western Blotting. MTT assay, flow cytometry, and scratch assay were used to verify the effects of INPP4B on proliferation, apoptosis and migration. Tumor formation experiment to verify the effect of INPP4B on tumor formation. Results In this study, we performed data mining analysis of HGSOC and LGSOC samples. We first identified 25 tumor suppressor genes associated with poor prognosis and survival in HGSOC. Further immune infiltration analysis of these 25 genes with the TIMER web tool showed that among the 25 genes, INPP4B had the most pronounced effect on CD8 + T-cell infiltration. In addition, detection of INPP4B expression by IHC staining in clinical samples indicated that the INPP4B level was significantly lower in ovarian cancer tissues and negatively related to patient survival. Moreover, knockdown of INPP4B accelerated ovarian cancer cell growth and migration in vitro and vivo. Finally, the genes related to INPP4B in ovarian cancer were mainly enriched in the immune response and inflammatory response. Conclusions INPP4B plays an important role in cell proliferation, cell growth, cell migration, apoptosis and immune infiltration in OC. The INPP4B gene, as a potential tumor suppressor gene, may become a biomarker and therapeutic target for ovarian cancer.