MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Classical Hodgkin lymphoma (cHL) presents treatment challenges, with a significant portion of advanced cases showing refractoriness to standard therapies.
• While microRNA (miRNA) signatures have been proposed for cHL, their direct correlation with patient prognosis remains largely undetermined.

Purpose of the Study:

• To identify and validate a miRNA signature associated with clinical outcome in advanced classical Hodgkin lymphoma.
• To investigate the functional role of specific miRNAs in cHL pathogenesis and therapeutic response.

Main Methods:

• Global miRNA expression profiling was performed on advanced cHL patient samples and cell lines.
• A 234-miRNA signature was identified, with a subset validated in an independent cohort using quantitative reverse transcription polymerase chain reaction.
• Multivariate Cox regression and cross-validation were employed to analyze the association between miRNA signatures and failure-free survival (FFS).

Main Results:

• A validated miRNA signature comprising MIR21, MIR30E, MIR30D, and MIR92B* identified two distinct risk groups with significantly different 5-year FFS rates (81% vs. 35.7%).
• Functional silencing of MIR21 and MIR30D in cHL cells enhanced sensitivity to doxorubicin-induced apoptosis.
• Deregulation of mitochondrial intrinsic and TP53-CDKN1A pathways was implicated in miRNA-associated therapeutic resistance.

Conclusions:

• Clinical outcome in classical Hodgkin lymphoma is significantly associated with a specific miRNA expression signature.
• MIR21 and MIR30D play a potential role in cHL pathogenesis and may influence therapeutic resistance, suggesting their utility as biomarkers or therapeutic targets.