A panel of circulating MicroRNAs detects uveal melanoma with high precision

Mitchell S. Stark, Elin S. Gray, Timothy Isaacs, Fred K. Chen, Michael Millward, Ashleigh McEvoy, Pauline Zaenker, Melanie Ziman, H. Peter Soyer, William J. Glasson, Sunil K. Warrier, Andrew L. Stark, Olivia J. Rolfe, Jane M. Palmer, Nicholas K. Hayward

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number12
JournalTranslational Vision Science and Technology
Volume8
Issue number6
DOIs
Publication statusPublished - Nov 2019

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MicroRNAs
Nevus
Blood
Biopsy
Real time systems
Decision making
Computer Systems
Uveal melanoma
Area Under Curve
Real-Time Polymerase Chain Reaction
Melanoma
Cross-Sectional Studies
Sensitivity and Specificity
Neoplasms

Cite this

Stark, Mitchell S. ; Gray, Elin S. ; Isaacs, Timothy ; Chen, Fred K. ; Millward, Michael ; McEvoy, Ashleigh ; Zaenker, Pauline ; Ziman, Melanie ; Soyer, H. Peter ; Glasson, William J. ; Warrier, Sunil K. ; Stark, Andrew L. ; Rolfe, Olivia J. ; Palmer, Jane M. ; Hayward, Nicholas K. / A panel of circulating MicroRNAs detects uveal melanoma with high precision. In: Translational Vision Science and Technology. 2019 ; Vol. 8, No. 6.
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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.",
keywords = "Biomarker, Diagnostic, Melanoma, MicroRNA, MiRNA, Prognostic, Uveal",
author = "Stark, {Mitchell S.} and Gray, {Elin S.} and Timothy Isaacs and Chen, {Fred K.} and Michael Millward and Ashleigh McEvoy and Pauline Zaenker and Melanie Ziman and Soyer, {H. Peter} and Glasson, {William J.} and Warrier, {Sunil K.} and Stark, {Andrew L.} and Rolfe, {Olivia J.} and Palmer, {Jane M.} and Hayward, {Nicholas K.}",
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Stark, MS, Gray, ES, Isaacs, T, Chen, FK, Millward, M, McEvoy, A, Zaenker, P, Ziman, M, Soyer, HP, Glasson, WJ, Warrier, SK, Stark, AL, Rolfe, OJ, Palmer, JM & Hayward, NK 2019, 'A panel of circulating MicroRNAs detects uveal melanoma with high precision' Translational Vision Science and Technology, vol. 8, no. 6, 12. https://doi.org/10.1167/tvst.8.6.12

A panel of circulating MicroRNAs detects uveal melanoma with high precision. / Stark, Mitchell S.; Gray, Elin S.; Isaacs, Timothy; Chen, Fred K.; Millward, Michael; McEvoy, Ashleigh; Zaenker, Pauline; Ziman, Melanie; Soyer, H. Peter; Glasson, William J.; Warrier, Sunil K.; Stark, Andrew L.; Rolfe, Olivia J.; Palmer, Jane M.; Hayward, Nicholas K.

In: Translational Vision Science and Technology, Vol. 8, No. 6, 12, 11.2019.

Research output: Contribution to journalArticle

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T1 - A panel of circulating MicroRNAs detects uveal melanoma with high precision

AU - Stark, Mitchell S.

AU - Gray, Elin S.

AU - Isaacs, Timothy

AU - Chen, Fred K.

AU - Millward, Michael

AU - McEvoy, Ashleigh

AU - Zaenker, Pauline

AU - Ziman, Melanie

AU - Soyer, H. Peter

AU - Glasson, William J.

AU - Warrier, Sunil K.

AU - Stark, Andrew L.

AU - Rolfe, Olivia J.

AU - Palmer, Jane M.

AU - Hayward, Nicholas K.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

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KW - Diagnostic

KW - Melanoma

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KW - Uveal

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