Alterations in patient plasma microRNA expression profiles following resection of metastatic melanoma

Abstract

Background and objectives: MicroRNAs (miRs) are noncoding RNAs that regulate protein translation and melanoma progression. Changes in plasma miR expression following surgical resection of metastatic melanoma are under-investigated. We hypothesize differences in miR expression exist following complete surgical resection of metastatic melanoma.

Methods: Blood collection pre- and post-surgical resection was performed in six individuals with solitary melanoma metastases. miR expression in extracted RNA was quantified using the NanoString nCounter Digital Analyzer.

Results: Pre- and post-surgical plasma samples contained 216 miRs with expression above baseline. Comparison of postsurgical to preresection samples revealed differential expression of 25 miRs: miR-let-7a, miR-let7g, miR-15a, miR-16, miR-22, miR-30b, miR-126, miR-140, miR-145, miR-148a, miR-150-5p, miR-191, miR-378i, miR-449c, miR-494, miR-513b, miR-548aa, miR-571, miR-587, miR-891b, miR-1260a, miR 1268a, miR-1976, miR-4268, miR-4454 (P < 0.05). Utilizing P < 0.0046 as a cutoff to control for one false positive among the 216 miRs revealed that postsurgical melanoma plasma samples had upregulation of miR-1260a (P = 0.0007) and downregulation of miR-150-5p (P = 0.0026) relative to pre-surgical samples.

Conclusions: Differential expression of miR-150-5p and miR-1260a is present in plasma following surgical resection of metastatic melanoma in this small sample (n = 6) of melanoma patients. Therefore, further investigation of these plasma miRs as noninvasive biomarkers for melanoma is warranted.

Keywords: NanoString; miR; miR-1260a; miR-150-5p; miRNA.

Figure 1. Volcano plot showing the fold change versus negative log of the p-value of differentially expressed miRNAs

The false discovery rate (FDR) cutoff imposed to define the statistical significance threshold of p<0.0046 (at y=2.337) indicates statistical significance of two miRs that passed this criterion, miR-1260a and miR-150-5p.

Figure 2. Gene interaction network generated using miR-150-5p experimentally validated gene targets

Only interactions with a high confidence interaction score are shown (0.9 or higher, scale of 0.1 to 1.0). Edges represent protein-protein interactions (PPI). PPI enrichment p-value = 0.00371. (Color legend: from curated databases = cyan blue, experimentally determined = magenta, textmining = green, coexpression = black).