Molecular Predictors May Help Determine Outcome for Melanoma Patients

Molecular Predictors May Help Determine Outcome for Melanoma Patients

June 18, 2015

MicroRNA (miRNA) profiling of samples from patients with metastatic melanoma who were treated with carboplatin/paclitaxel (CP) identified significantly higher expression of a specific microRNA (miR-659-3p) that was associated with longer progression-free survival (P = .008).

MicroRNA (miRNA) profiling of samples from patients with metastatic melanoma who were treated with carboplatin/paclitaxel (CP) identified significantly higher expression of a specific microRNA (miR-659-3p) that was associated with longer progression-free survival (P = .008).

Using a progression-free survival (PFS) cutoff of 4 months (the median PFS for all patients in the study), higher miR-659-3p expression was prognostic of longer PFS (P = .03), according to results published in Clinical Epigenetics.1

“This novel integrative analysis suggests miR-659-3p as a candidate biomarker of response in MM (metastatic melanoma) patients treated with platinum-based chemotherapy and may serve to improve patient selection. To our knowledge, our study is the first to identify a miRNA species as a predictor of therapy outcome in metastatic melanoma,” wrote Liza Villaruz, MD, Assistant Professor of Medicine at the University of Pittsburgh School of Medicine, in the Division of Hematology/Oncology, and colleagues.

In order to identify prognostic indicators for response to CP therapy, samples from 115 patients with metastatic melanoma who participated in the phase III trial, ECOG Study E2603, were analyzed for miRNA and messenger RNA (mRNA) expression profiles. The trial examined the combination of the targeted therapy sorafenib (Sutent) with platinum-based chemotherapy, and all patients received CP therapy. The expression of miR-659-3p did not significantly differ based on treatment arm.

The functional significance of miR-659-3p in melanoma is unclear. The miRNA is known to bind the gene for progranulin, a protein implicated in frontotemporal dementia risk.

“Recalcitrance of melanoma to chemotherapy is a significant issue due to limited response rates and lack of predictive biomarkers of chemotherapy benefit,” the authors wrote.

Response rates to CP therapy among patients with MM typically range from 18% to 20% in first-line and 11% to 12% in second-line settings. Biomarkers for response and survival would facilitate more efficient use of chemotherapy and may improve outcomes.

MiRNAs are short (22 nucleotides), noncoding RNAs that post-transcriptionally regulate gene expression. MiRNAs have been shown to regulate genes for tumor suppression, cell metastasis, and oncogenesis. Studies have shown that the specific miRNAs have prognostic implications in melanoma as well.

A related analysis of gene expression via mRNA levels showed that PLXNB1, the gene for plexin B1, was significantly associated with shorter PFS. This gene had previously been shown to play a role in melanoma, particularly in resistance to cisplatin-induced apoptosis in melanoma cell lines. 

 

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