Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients

Nathaniel H. Fleming, Judy Zhong, Inês Pires Da Silva, Eleazar Vega Saenz De Miera, Bobbi Brady, Sung Won Han, Doug Hanniford, Jinhua Wang, Richard L. Shapiro, Eva Hernando, Iman Osman

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

BACKGROUND: Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence. METHODS: Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n=201; independent validation, n=82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n=225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology. RESULTS: Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P<.001; validation RFS, P<.001; OS, P=.005). Serum miR-15b levels significantly increased over time in recurrent patients (P<.001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17). CONCLUSIONS: Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalCancer
Volume121
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Fingerprint

MicroRNAs
Melanoma
Recurrence
Serum
Survival
Atlases
Genome
Polymerase Chain Reaction

Keywords

  • Biomarkers
  • Melanoma
  • MicroRNAs
  • Recurrence
  • Serum markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fleming, N. H., Zhong, J., Da Silva, I. P., De Miera, E. V. S., Brady, B., Han, S. W., ... Osman, I. (2015). Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. Cancer, 121(1), 51-59. https://doi.org/10.1002/cncr.28981

Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. / Fleming, Nathaniel H.; Zhong, Judy; Da Silva, Inês Pires; De Miera, Eleazar Vega Saenz; Brady, Bobbi; Han, Sung Won; Hanniford, Doug; Wang, Jinhua; Shapiro, Richard L.; Hernando, Eva; Osman, Iman.

In: Cancer, Vol. 121, No. 1, 01.01.2015, p. 51-59.

Research output: Contribution to journalArticle

Fleming, NH, Zhong, J, Da Silva, IP, De Miera, EVS, Brady, B, Han, SW, Hanniford, D, Wang, J, Shapiro, RL, Hernando, E & Osman, I 2015, 'Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients', Cancer, vol. 121, no. 1, pp. 51-59. https://doi.org/10.1002/cncr.28981
Fleming NH, Zhong J, Da Silva IP, De Miera EVS, Brady B, Han SW et al. Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. Cancer. 2015 Jan 1;121(1):51-59. https://doi.org/10.1002/cncr.28981
Fleming, Nathaniel H. ; Zhong, Judy ; Da Silva, Inês Pires ; De Miera, Eleazar Vega Saenz ; Brady, Bobbi ; Han, Sung Won ; Hanniford, Doug ; Wang, Jinhua ; Shapiro, Richard L. ; Hernando, Eva ; Osman, Iman. / Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. In: Cancer. 2015 ; Vol. 121, No. 1. pp. 51-59.
@article{29a20eccbb224ea49feb1948725e5e29,
title = "Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients",
abstract = "BACKGROUND: Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence. METHODS: Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n=201; independent validation, n=82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n=225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology. RESULTS: Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P<.001; validation RFS, P<.001; OS, P=.005). Serum miR-15b levels significantly increased over time in recurrent patients (P<.001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17). CONCLUSIONS: Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance.",
keywords = "Biomarkers, Melanoma, MicroRNAs, Recurrence, Serum markers",
author = "Fleming, {Nathaniel H.} and Judy Zhong and {Da Silva}, {In{\^e}s Pires} and {De Miera}, {Eleazar Vega Saenz} and Bobbi Brady and Han, {Sung Won} and Doug Hanniford and Jinhua Wang and Shapiro, {Richard L.} and Eva Hernando and Iman Osman",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/cncr.28981",
language = "English",
volume = "121",
pages = "51--59",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients

AU - Fleming, Nathaniel H.

AU - Zhong, Judy

AU - Da Silva, Inês Pires

AU - De Miera, Eleazar Vega Saenz

AU - Brady, Bobbi

AU - Han, Sung Won

AU - Hanniford, Doug

AU - Wang, Jinhua

AU - Shapiro, Richard L.

AU - Hernando, Eva

AU - Osman, Iman

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND: Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence. METHODS: Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n=201; independent validation, n=82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n=225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology. RESULTS: Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P<.001; validation RFS, P<.001; OS, P=.005). Serum miR-15b levels significantly increased over time in recurrent patients (P<.001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17). CONCLUSIONS: Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance.

AB - BACKGROUND: Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence. METHODS: Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n=201; independent validation, n=82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n=225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology. RESULTS: Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P<.001; validation RFS, P<.001; OS, P=.005). Serum miR-15b levels significantly increased over time in recurrent patients (P<.001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17). CONCLUSIONS: Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance.

KW - Biomarkers

KW - Melanoma

KW - MicroRNAs

KW - Recurrence

KW - Serum markers

UR - http://www.scopus.com/inward/record.url?scp=84918830062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918830062&partnerID=8YFLogxK

U2 - 10.1002/cncr.28981

DO - 10.1002/cncr.28981

M3 - Article

C2 - 25155861

AN - SCOPUS:84918830062

VL - 121

SP - 51

EP - 59

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 1

ER -