MARCO is a potential prognostic and immunotherapy biomarker

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Macrophage receptor with collagenous structure (MARCO) is an immune checkpoint on tumor-associated macrophages with antitumor properties.
• The prognostic and immunotherapeutic implications of MARCO in various cancers require urgent investigation.

Purpose of the Study:

• To comprehensively investigate the association between MARCO expression and patient prognosis across diverse cancer types.
• To explore the relationship between MARCO, immune infiltration, and response to immune checkpoint inhibitor (ICI) therapy.
• To identify potential signaling pathways modulated by MARCO in the tumor microenvironment.

Main Methods:

• Utilized TCGA and GTEx databases for MARCO expression analysis in cancer tissues.
• Assessed MARCO's prognostic value using PrognoScan and KM Plotter databases.
• Analyzed MARCO's correlation with immune infiltration, mutation profiles, and pathways via TIMER2.0, GEPIA, cBioPortal, and Gene Set Enrichment Analysis (GSEA).
• Employed R language for data visualization.

Main Results:

• MARCO expression significantly impacts patient prognosis, with differential expression observed between tumor and normal tissues.
• High MARCO expression correlated with poorer overall survival (OS) in bladder urothelial carcinoma, breast invasive carcinoma, lung squamous cell carcinoma, colon adenocarcinoma, and prostate adenocarcinoma.
• Conversely, high MARCO expression was associated with better progression-free interval (PFI) in brain lower-grade glioma and skin cutaneous melanoma.
• MARCO positively correlated with immune checkpoints CD80, CD86, and LAIR1 in most cancers and showed the highest microsatellite instability (MSI) in colon adenocarcinoma.
• Patients with high MARCO expression demonstrated improved outcomes following ICI treatment in skin cutaneous melanoma.
• GSEA revealed significant associations between MARCO and TNF/NFκB, KRAS, PI3K/AKT/mTOR, IL-6-STAT3, TGFβ, and p53 signaling pathways.

Conclusions:

• MARCO serves as a significant biomarker influencing clinical outcomes and immune characteristics in various cancers.
• MARCO expression patterns provide insights into tumor progression and response to immunotherapy.
• MARCO represents a promising target for developing novel cancer immunotherapeutic strategies.