Proteomic surfaceome analysis of mesothelioma

Area of Science:

• Proteomics
• Biomarker Discovery
• Oncology

Background:

• Malignant pleural mesothelioma (MPM) diagnosis requires new, reliable markers.
• Existing diagnostic methods have limitations, necessitating novel approaches.

Purpose of the Study:

• To identify and validate novel cell surface N-glycoproteins as potential diagnostic markers for MPM.
• To differentiate MPM from lung adenocarcinoma (ADCA) using proteomic and transcriptomic analyses.

Main Methods:

• Utilized antibody-independent mass-spectrometry based cell surface capturing (CSC) technology for N-glycoprotein analysis.
• Employed high throughput low density microarrays (LDAs) for secondary screening and validation.
• Integrated proteomic and transcriptomic data for marker identification.

Main Results:

• Quantitative CSC analysis revealed distinct surfaceome profiles between MPM and ADCA cell lines.
• Nineteen overregulated N-glycoproteins were identified in MPM surfaceomes.
• Thy-1/CD90 (THY1) and Teneurin-2 (ODZ2) were identified as promising marker candidates.
• Immunohistochemistry validated Thy-1/CD90 expression in MPM tissues.

Conclusions:

• Thy-1/CD90 and Teneurin-2 are potential protein markers for discriminating MPM from ADCA.
• The combined proteomic and transcriptomic approach is effective for identifying and pre-clinically selecting MPM marker candidates.
• This study provides a foundation for developing new protein-based diagnostic assays for MPM.