Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling

Lori A. Worley, Meghan D. Long, Michael D. Onken, J. William Harbour

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Uveal (ocular) melanoma is a highly aggressive cancer that leads to metastatic death in up to half of patients despite successful local therapy. Biomarkers of metastatic risk are critically needed to institute new adjuvant treatment strategies in high-risk patients. Previously, we showed that two prognostically significant molecular subtypes of uveal melanoma could be identified based on gene expression profiling of the primary tumor. In this study, we investigated the value of micro-RNA (miRNA) expression patterns in predicting metastatic risk. A genome-wide, microarray-based approach was used to screen for differentially expressed miRNAs using the Agilent miRNA microarray (Agilent Technologies, Foster City, California, USA) platform containing probes for 470 human miRNAs. Unsupervised analysis was performed using principal component analysis, and supervised analysis was performed using significance analysis of microarrays. Tumors readily clustered based on miRNA expression into two groups that corresponded to the gene expression-based subtypes: class 1 (low metastatic risk) and class 2 (high metastatic risk). The most significant discriminators were let-7b and miR-199a, and the expression of these miRNAs was validated by quantitative PCR. A classifier that included the top six miRNA discriminators accurately distinguished class 1 from class 2 tumors with 100% sensitivity and specificity. miRNA expression may represent a highly accurate biomarker for metastatic risk in uveal melanoma. In addition, these results may provide new insights into the role of miRNAs in tumor progression and the metastatic phenotype.

Original languageEnglish
Pages (from-to)184-190
Number of pages7
JournalMelanoma Research
Volume18
Issue number3
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

MicroRNAs
Neoplasm Metastasis
Neoplasms
Biomarkers
Uveal melanoma
Gene Expression Profiling
Microarray Analysis
Principal Component Analysis
Genome
Technology
Phenotype
Gene Expression
Sensitivity and Specificity
Polymerase Chain Reaction
Therapeutics

Keywords

  • hsa-let-7b
  • hsa-miR-199a
  • Metastasis
  • Micro-RNA
  • Prognosis
  • Uveal melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Dermatology

Cite this

Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling. / Worley, Lori A.; Long, Meghan D.; Onken, Michael D.; William Harbour, J.

In: Melanoma Research, Vol. 18, No. 3, 01.06.2008, p. 184-190.

Research output: Contribution to journalArticle

Worley, Lori A. ; Long, Meghan D. ; Onken, Michael D. ; William Harbour, J. / Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling. In: Melanoma Research. 2008 ; Vol. 18, No. 3. pp. 184-190.
@article{42d550d893744ec29b806f950e54a8b0,
title = "Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling",
abstract = "Uveal (ocular) melanoma is a highly aggressive cancer that leads to metastatic death in up to half of patients despite successful local therapy. Biomarkers of metastatic risk are critically needed to institute new adjuvant treatment strategies in high-risk patients. Previously, we showed that two prognostically significant molecular subtypes of uveal melanoma could be identified based on gene expression profiling of the primary tumor. In this study, we investigated the value of micro-RNA (miRNA) expression patterns in predicting metastatic risk. A genome-wide, microarray-based approach was used to screen for differentially expressed miRNAs using the Agilent miRNA microarray (Agilent Technologies, Foster City, California, USA) platform containing probes for 470 human miRNAs. Unsupervised analysis was performed using principal component analysis, and supervised analysis was performed using significance analysis of microarrays. Tumors readily clustered based on miRNA expression into two groups that corresponded to the gene expression-based subtypes: class 1 (low metastatic risk) and class 2 (high metastatic risk). The most significant discriminators were let-7b and miR-199a, and the expression of these miRNAs was validated by quantitative PCR. A classifier that included the top six miRNA discriminators accurately distinguished class 1 from class 2 tumors with 100{\%} sensitivity and specificity. miRNA expression may represent a highly accurate biomarker for metastatic risk in uveal melanoma. In addition, these results may provide new insights into the role of miRNAs in tumor progression and the metastatic phenotype.",
keywords = "hsa-let-7b, hsa-miR-199a, Metastasis, Micro-RNA, Prognosis, Uveal melanoma",
author = "Worley, {Lori A.} and Long, {Meghan D.} and Onken, {Michael D.} and {William Harbour}, J.",
year = "2008",
month = "6",
day = "1",
doi = "10.1097/CMR.0b013e3282feeac6",
language = "English",
volume = "18",
pages = "184--190",
journal = "Melanoma Research",
issn = "0960-8931",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling

AU - Worley, Lori A.

AU - Long, Meghan D.

AU - Onken, Michael D.

AU - William Harbour, J.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Uveal (ocular) melanoma is a highly aggressive cancer that leads to metastatic death in up to half of patients despite successful local therapy. Biomarkers of metastatic risk are critically needed to institute new adjuvant treatment strategies in high-risk patients. Previously, we showed that two prognostically significant molecular subtypes of uveal melanoma could be identified based on gene expression profiling of the primary tumor. In this study, we investigated the value of micro-RNA (miRNA) expression patterns in predicting metastatic risk. A genome-wide, microarray-based approach was used to screen for differentially expressed miRNAs using the Agilent miRNA microarray (Agilent Technologies, Foster City, California, USA) platform containing probes for 470 human miRNAs. Unsupervised analysis was performed using principal component analysis, and supervised analysis was performed using significance analysis of microarrays. Tumors readily clustered based on miRNA expression into two groups that corresponded to the gene expression-based subtypes: class 1 (low metastatic risk) and class 2 (high metastatic risk). The most significant discriminators were let-7b and miR-199a, and the expression of these miRNAs was validated by quantitative PCR. A classifier that included the top six miRNA discriminators accurately distinguished class 1 from class 2 tumors with 100% sensitivity and specificity. miRNA expression may represent a highly accurate biomarker for metastatic risk in uveal melanoma. In addition, these results may provide new insights into the role of miRNAs in tumor progression and the metastatic phenotype.

AB - Uveal (ocular) melanoma is a highly aggressive cancer that leads to metastatic death in up to half of patients despite successful local therapy. Biomarkers of metastatic risk are critically needed to institute new adjuvant treatment strategies in high-risk patients. Previously, we showed that two prognostically significant molecular subtypes of uveal melanoma could be identified based on gene expression profiling of the primary tumor. In this study, we investigated the value of micro-RNA (miRNA) expression patterns in predicting metastatic risk. A genome-wide, microarray-based approach was used to screen for differentially expressed miRNAs using the Agilent miRNA microarray (Agilent Technologies, Foster City, California, USA) platform containing probes for 470 human miRNAs. Unsupervised analysis was performed using principal component analysis, and supervised analysis was performed using significance analysis of microarrays. Tumors readily clustered based on miRNA expression into two groups that corresponded to the gene expression-based subtypes: class 1 (low metastatic risk) and class 2 (high metastatic risk). The most significant discriminators were let-7b and miR-199a, and the expression of these miRNAs was validated by quantitative PCR. A classifier that included the top six miRNA discriminators accurately distinguished class 1 from class 2 tumors with 100% sensitivity and specificity. miRNA expression may represent a highly accurate biomarker for metastatic risk in uveal melanoma. In addition, these results may provide new insights into the role of miRNAs in tumor progression and the metastatic phenotype.

KW - hsa-let-7b

KW - hsa-miR-199a

KW - Metastasis

KW - Micro-RNA

KW - Prognosis

KW - Uveal melanoma

UR - http://www.scopus.com/inward/record.url?scp=43649087713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43649087713&partnerID=8YFLogxK

U2 - 10.1097/CMR.0b013e3282feeac6

DO - 10.1097/CMR.0b013e3282feeac6

M3 - Article

C2 - 18477892

AN - SCOPUS:43649087713

VL - 18

SP - 184

EP - 190

JO - Melanoma Research

JF - Melanoma Research

SN - 0960-8931

IS - 3

ER -