The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis.
The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are < 15%. Hence, melanoma detection in earlier stages (stages I-III) maximises the chances of patient survival. We measured the expression of a panel of 17 microRNAs (miRNAs) (MELmiR-17) in melanoma tissues (stage III; n = 76 and IV; n = 10) and serum samples (collected from controls with no melanoma, n = 130; and patients with melanoma (stages I/II, n = 86; III, n = 50; and IV, n = 119)) obtained from biobanks in Australia and Germany. In melanoma tissues, members of the 'MELmiR-17' panel were found to be predictors of stage, recurrence, and survival. Additionally, in a minimally-invasive blood test, a seven-miRNA panel (MELmiR-7) detected the presence of melanoma (relative to controls) with high sensitivity (93%) and specificity (≥ 82%) when ≥ 4 miRNAs were expressed. Moreover, the 'MELmiR-7' panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood = 11, p < 0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa-c/IV M1a-b) to detect relapse following surgical or adjuvant treatment.
Oncogenomics Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia ; School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
Mitchell S
MS
Stark
Statistics Unit, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia ; Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia.
Kerenaftali
K
Klein
Department of Dermatology, University Medical Center, Tubingen, Germany.
Benjamin
B
Weide
Melanoma Institute Australia, Sydney, NSW, Australia ; The University of Sydney, Sydney Medical School, Sydney, Australia.
Lauren E
LE
Haydu
Department of Dermatology, University Medical Center, Tubingen, Germany ; Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Annette
A
Pflugfelder
Surgical Oncology Group, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia.
Yue Hang
YH
Tang
Oncogenomics Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia.
Jane M
JM
Palmer
Cancer Control Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia.
David C
DC
Whiteman
Melanoma Institute Australia, Sydney, NSW, Australia ; The University of Sydney, Sydney Medical School, Sydney, Australia.
Richard A
RA
Scolyer
Melanoma Institute Australia, Sydney, NSW, Australia ; The University of Sydney, Sydney Medical School, Sydney, Australia.
Graham J
GJ
Mann
Melanoma Institute Australia, Sydney, NSW, Australia ; The University of Sydney, Sydney Medical School, Sydney, Australia.
John F
JF
Thompson
Melanoma Institute Australia, Sydney, NSW, Australia ; The University of Sydney, Sydney Medical School, Sydney, Australia.
Georgina V
GV
Long
Surgical Oncology Group, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia.
Andrew P
AP
Barbour
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
H Peter
HP
Soyer
Department of Dermatology, University Medical Center, Tubingen, Germany.
Claus
C
Garbe
School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
Adrian
A
Herington
School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
Pamela M
PM
Pollock
Oncogenomics Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4029, Australia.
Nicholas K
NK
Hayward
D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology*; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D055815:Young Adult
D035683:MicroRNAs
AGO2, argonaute RISC catalytic component 2; AJCC, American Joint Committee on Cancer; AUC, area under the curve; AUROC, area under the receiver operator curve; Biomarker; CI, confidence interval; Ct, threshold cycle; DOR, diagnostic odds ratio; Diagnostic; FFPE, formalin-fixed paraffin-embedded; HR, hazard ratio; LDH, lactate dehydrogenase; M1a, metastasis to skin, subcutaneous (below the skin) tissue, or lymph nodes in distant parts of the body, with a normal blood LDH level; M1b, metastasis to the lungs, with a normal blood LDH level; M1c, metastasis to any other organs, OR distant spread to any site along with an elevated blood LDH level; MIA, Melanoma Institute of Australia; Melanoma; MiRNA; MicroRNA; N stage, nodal or number of lymph nodes stage; NA, not applicable; NM, nodular melanoma; OR, odds ratio; PD1, programmed cell death protein; Prognostic; RNA, ribonucleic acid; S100B, S100 calcium-binding protein B; SMM, superficial spreading melanoma; USA, United States of America; miR, microRNA; miRNA, microRNA