IFI44 Orchestrates an IL-10-Driven M2 Macrophage Program in Breast Cancer: An Immune Prognostic Signature

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• The role of Interferon-induced protein 44 (IFI44) in breast cancer (BC) pathogenesis is not well understood, despite its known involvement in autoimmune diseases.
• This study investigates the immune-related functions and prognostic value of IFI44 in the context of breast cancer.

Purpose of the Study:

• To elucidate the function of IFI44 in breast cancer progression.
• To explore the association between IFI44 expression and M2 macrophage infiltration.
• To develop a predictive model for breast cancer prognosis and treatment response based on IFI44 and M2 macrophage markers.

Main Methods:

• Bio-informatics analyses including CIBERSORT, ESTIMATE, TIMER2, and GEPIA2 were employed.
• In vitro experiments assessed breast cancer cell proliferation, migration, and invasion.
• LASSO Cox regression was used to construct an IFI44-related M2 macrophage signature (IMS).
• Survival analysis, ROC curves, and drug sensitivity data evaluated the IMS's prognostic performance and association with treatment response.

Main Results:

• IFI44 was found to be highly expressed in breast cancer and correlated with poor prognosis.
• Downregulation of IFI44 inhibited M2 macrophage proliferation, a process reversible by IL-10.
• The developed IMS, comprising four genes, accurately predicted overall survival in breast cancer patients and showed potential in pan-cancer analysis.
• The IMS also demonstrated predictive capabilities for prognosis and immune scores across multiple cancer types.

Conclusions:

• IFI44 promotes breast cancer progression and M2 macrophage infiltration via an IL-10-dependent pathway.
• IFI44 emerges as a potential therapeutic target for breast cancer immunotherapy.
• The IFI44-based IMS offers a valuable tool for predicting patient prognosis and guiding treatment decisions in cancer.