To explore molecular subtypes of advanced cutaneous T-cell lymphoma (CTCL) and identify potential biomarkers associated with treatment response and disease progression.
Approach:
Sample Collection: Tumor cell-enriched regions of 33 advanced CTCL samples from 31 patients were obtained using laser capture microdissection.
Profiling: Integrated proteomic and transcriptomic profiling was performed on the collected samples.
Validation: Selected biomarkers were validated via immunohistochemistry.
Key Findings:
Three molecular subtypes of advanced CTCL were identified: intracellular signaling subtype, metabolic subtype, and extracellular matrix remodeling subtype.
The PI3K-AKT-mTOR pathway was upregulated in the intracellular signaling subtype, with phospho-AKT levels correlating with response to PI3Kδ inhibitor therapy.
Potential biomarkers for predicting treatment responsiveness include CTSB, GSTO1, and WDFY4, while GOLGA1 and STIP1 may predict disease progression.
Interpretation:
Limitations:
The findings require validation in larger cohorts to confirm the associations between biomarkers and clinical outcomes.
