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Integrative Raman Spectroscopy and Multi-Omics Analysis of Lipid and Matrix Protein Heterogeneity in Triple-Negative
Elnaz Sheikh1, Khudeja Salim2, Praveen Kumar Guttula1
1Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
Triple-negative breast cancer (TNBC) shows increased unsaturated fatty acids and altered proteins like collagen and fibronectin. Raman microspectroscopy accurately profiles these molecular changes in TNBC tumors, aiding in understanding tumor progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Lipid alterations are implicated in breast cancer proliferation and progression.
- Triple-negative breast cancer (TNBC) is an aggressive subtype with distinct molecular characteristics.
- Understanding the molecular landscape of TNBC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate molecular differences in lipids and proteins between TNBC tumors and matched normal breast tissues.
- To evaluate the efficacy of Raman microspectroscopy combined with LC-MS for profiling these molecular changes.
- To identify key metabolic and extracellular matrix alterations associated with TNBC.
Main Methods:
- Comparative analysis of TNBC and normal breast tissues using Raman microspectroscopy and liquid chromatography-mass spectrometry (LC-MS).
- Direct classical least-squares (DCLS) approach for spectral analysis of fatty acids and proteins.
- Proteomics and lipidomics analyses to characterize metabolic alterations.
- Network and pathway analyses to understand coordinated molecular changes.
Main Results:
- TNBC tissues exhibited significantly higher levels of unsaturated fatty acids (ω-3, ω-6), including EPA, DHA, AA, and LA.
- Specific protein alterations were observed: decreased collagen I, III, IV, and laminin; increased collagen V and fibronectin.
- Upregulation of phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) lipid species in TNBC.
- Raman microspectroscopy demonstrated accuracy in spatial profiling of lipids and proteins.
Conclusions:
- Coordinated changes in lipid metabolism and extracellular matrix (ECM) remodeling are characteristic of TNBC.
- Raman microspectroscopy is a valuable non-destructive tool for spatial molecular profiling of breast cancer tissues.
- Spatial mapping of extracellular components can elucidate mechanisms driving TNBC progression and heterogeneity.
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