Deciphering the Role of KIF18A in Osteosarcoma Progression: An Integrative Analysis and Experimental Validation

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Osteosarcoma (OS) is a highly aggressive bone cancer known for metastasis.
• Identifying molecular drivers is crucial for effective OS therapies.
• The role of KIF18A in OS progression and metastasis is largely unknown.

Purpose of the Study:

• To investigate the role of KIF18A in osteosarcoma (OS) development and progression.
• To explore KIF18A as a potential prognostic biomarker and therapeutic target in OS.

Main Methods:

• Differential gene expression analysis of OS datasets (GSE126209, TARGET).
• Functional assays (in vitro and in vivo) to assess KIF18A's impact on OS cell behavior and tumor growth.
• Pathway enrichment analysis (GSEA), tumor immune microenvironment analysis (CIBERSORT), and drug sensitivity profiling.

Main Results:

• KIF18A is significantly upregulated in OS tissues and associated with metastasis and poor outcomes.
• KIF18A promotes OS cell proliferation, invasion, migration, and inhibits apoptosis in vitro.
• KIF18A knockdown suppresses tumor growth in vivo and correlates with an immunosuppressive tumor microenvironment.

Conclusions:

• KIF18A acts as a pivotal oncogene in OS, driving progression and metastasis.
• KIF18A is a promising prognostic biomarker and therapeutic target for osteosarcoma.
• KIF18A dysregulation is linked to oncogenic pathways, immune suppression, and potential immunotherapy resistance.