Dataset Information

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

ABSTRACT:

Purpose

To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi.

Methods

We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system.

Results

A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point.

Conclusions

This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel's high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features.

Translational relevance

Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.

SUBMITTER: Stark MS

PROVIDER: S-EPMC6855372 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

Stark Mitchell S MS Gray Elin S ES Isaacs Timothy T Chen Fred K FK Millward Michael M McEvoy Ashleigh A Zaenker Pauline P Ziman Melanie M Soyer H Peter HP Glasson William J WJ Warrier Sunil K SK Stark Andrew L AL Rolfe Olivia J OJ Palmer Jane M JM Hayward Nicholas K NK

Translational vision science & technology 20191114 6

<h4>Purpose</h4>To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi.<h4>Methods</h4>We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (<i>n</i> = 10), localized uveal melanoma (<i>n</i> = 50), or metastatic uveal melanoma (<i>n</i> = 5). Levels of 17 miRNAs were measur ...[more]

PMID: 31737436

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Project description:IntroductionApproximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.Materials and methodsThis was a single-arm, multicenter study in patients with high-risk UM who received definitive treatment of primary disease and had no evidence of metastasis. Patients were consecutively enrolled to receive 12 four-week cycles of adjuvant crizotinib at a starting dose of 250mg twice daily and were subsequently monitored for 36 months. The primary outcome of this study was to assess recurrence-free survival (RFS) of patients with high-risk UM who received adjuvant crizotinib.Results34 patients enrolled and received at least one dose of crizotinib. Two patients were unevaluable due to early withdrawal and loss to follow-up, leaving 32 patients evaluable for efficacy. Eight patients (25%) did not complete the planned 48-week course of treatment due to disease recurrence (n=5) or toxicity (n=3). All patients experienced at least one adverse event (AE), with 11/34 (32%) experiencing a Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 AE. After a median duration of follow up of 47.1 months, 21 patients developed distant recurrent disease. The median RFS was 34.9 months (95% CI (Confidence Interval), 23-55 months), with a 32-month recurrence rate of 50% (95% CI, 33-67%). Analysis of protein contents from peripheral blood extracellular vesicles in a subset of patient samples from baseline, on-treatment, and off-treatment, revealed a change in protein content associated with crizotinib exposure, however without a clear association with disease outcome.ConclusionsThe use of adjuvant crizotinib in patients with high-risk UM did not result in improved RFS when compared to historical controls. Analysis of blood extracellular vesicles revealed changes in protein content associated with treatment, raising the possibility of future use as a biomarker. Further investigation of adjuvant treatment options are necessary for this challenging disease.

Project description:PurposeUveal melanoma is the most common intraocular primary tumor, involving iris, ciliary body and choroid. More than 90% of the patients develop hepatic metastasis with an average survival time of 7 months. We have used formalin fixed paraffin embedded sections to validate the presence of monosomy 3, an accurate predictor of metastasis, chromosome 8 isochromosome (8q22), and 1p36 deletion. This study also tested the presence of oncomirs in uveal melanoma samples by microRNA (miRNA) expression profiling.MethodsChromogenic in situ hybridization (CISH) was performed in formalin fixed, paraffin embedded sections of uveal melanoma to analyze chromosome 1, 3, and 8 aberrations (n=60). MicroRNA (miRNA) expression profiling was done on paraffin sections of invasive tumor with liver metastasis (n=1) and non invasive tumor (n=1) in biological duplicates. Samples for miRNA expression profiling were identified based on case registry and the harboring of monosomy 3 by CISH.ResultsA significant correlation (p=0.05) between metastasizing and non-metastasizing melanoma harboring chromosomal aberrations- monosomy3, c-myc, and 1p36 was observed by Pearson's correlation. A significant correlation was observed in monosomy 3 and 1p36 positive cases in the tumor samples (p=0.039). No significance was observed between monosomy 3 and c-myc positive cases. No significance (p=0.096) was observed between c-myc amplification and trisomy (extra whole chromosome 8). MicroRNA expression profiling revealed the presence of 19 miRNAs expressed in non-metastasizing melanoma and absent in metastasizing melanoma. Eleven miRNAs were found to be expressed in metastasizing melanoma and absent in non-metastasizing melanoma. Genes targeted by the miRNAs were found to be present in chromosomal regions 8p22, 13q, and 17p but were often found to be deleted.ConclusionsThis technique can be applied to routine pathology using archival specimens to identify patients with monosomy 3. We were able to perform CISH in all the cases except the heavily pigmented tumors, where dots were observed but were not assessed. Initial studies on microRNA have revealed their role as oncomirs in both metastasizing and non-metastasizing melanomas. Further studies may provide insights into their role in tumor progression and facilitate metastatic phenotype analysis.

Dataset Information

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

Similar Datasets

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