A 4-microRNA signature is significantly associated with progression-free survival in patients with advanced melanoma treated with neoadjuvant ipilimumab, a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2016 has shown.1
For the study, researchers sought to determine whether microRNA expression profiles have therapeutic predictive value in patients with regionally advanced melanoma treated with the CTLA-4 inhibitor. Researchers treated patients with ipilimumab 10 mg/kg intravenously every 3 weeks for 2 doses prior to surgery and performed microRNA expression profiling on tumor biopsies from 30 patients.
Results showed that an expression profile consisting of a 4-microRNA signature was associated with improved progression-free survival. The signature consisted of microR-34c, mciroR-711, microR-641, and microR-22.
MicroR-34c has been reported to suppress cancer growth and invasion, while microR-711 has been showed to be a prognostic marker in cutaneous T-cell lymphoma and to target and inhibit Heat Shock Protein 70, which is highly expressed in melanoma. MicroR-641 actives MAPK by targeting NF1 and microR-22 has been reported to function as a tumor suppressor.
Researchers also found that the target genes for the 4-microRNA signature are biologically relevant and important, with them being statistically significantly enriched for numerous cancer-related signaling pathways, including regulation of cell proliferation, regulation of apoptosis, MAPK signaling pathway, and positive regulation of T-cell activation.
These findings ultimately warrant further investigation with regard to ipilimumab and other immunotherapeutic agents.
- Tarhini A, Vallabhaneni P, Floros T, et al. A tumor and immune related miRNA signature predicts progression-free survival of melanoma patients treated with ipilimumab. Poster presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.