Multidimensional Proteomic Landscape Reveals Distinct Activated Pathways Between Human Brain Tumors

Area of Science:

• Oncology
• Proteomics
• Molecular Biology

Background:

• Brain tumors, including brain metastases (BrMs) and gliomas, present significant mortality and clinical challenges.
• Current understanding of the molecular pathophysiology of these distinct brain tumors remains incomplete.
• Multidimensional proteomic analysis offers a pathway to elucidate shared and tumor-specific characteristics.

Purpose of the Study:

• To present a multidimensional proteomic landscape of BrMs and gliomas at tissue and plasma levels.
• To infer tumor-specific molecular pathophysiology and identify novel biomarkers.
• To discover potential therapeutic targets for precision medicine.

Main Methods:

• Proteomic analysis of tissue and plasma samples from BrMs and gliomas.
• Differential pathway analysis, focusing on the PI3K-Akt signaling pathway.
• Identification and validation of potential protein and phosphosite biomarkers.

Main Results:

• Significant molecular disparities identified between BrMs and gliomas, including distinct PI3K-Akt pathway activation.
• Novel proteins (e.g., NSUN2, TM9SF3) and phosphosites (e.g., PRKCG_S330) correlated with clinical traits, suggesting potential immunohistochemistry biomarkers.
• Altered phosphosites and glycosites on FN1 identified as potential therapeutic targets.
• Three biomarker panels (19 biomarkers total) developed for discriminating brain tumors from controls.

Conclusions:

• This comprehensive proteomic dataset provides valuable insights into brain tumor pathophysiology.
• Identified biomarkers offer potential for improved diagnosis and prognosis of BrMs and gliomas.
• Findings support the advancement of targeted therapy and immunotherapy in precision oncology for brain cancer patients.