Correlation of interferon-induced gene IFIT1 with immune infiltration and prognosis in ovarian cancer

Objective To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) with immune infiltration and prognosis of ovarian cancer (OC). Methods GEO database was employed to select the tumor immune related genes, and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis. The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA, Human Protein Atlas, and Timer databases. The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database. In addition, based on David database, GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases. Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually. Finally, after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA, the tumor growth was observed in the transplanted nude mice, and infiltration of neutrophils was observed with immunohistochemical assay. Results FIT1, a tumor immune gene, selected from the GEO database, Kaplan-Meier and Prognoscan databases, was negatively correlated with the OC prognosis. GEPIA, Human Protein Atlas, Timer database, and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues, and had no obvious correlation with tumor stage and grade. Analysis in String, Genemania, and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5' oligonucleotide synthase, virus defense, and innate immunity, and other processes. The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8+T cells, B cells, dendritic cells, neutrophils, and macrophage in OC, with neutrophils having the most significant correlation. Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC (P < 0.05). RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice (P < 0.05) and reduced neutrophil infiltration in the xenograft tissues. Conclusion IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.