1. Characterisation and validation of Mel38; A multi-tissue microRNA signature of cutaneous melanoma
- Author
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Sian Fereday, Ryan van Laar, and Mitchel Lincoln
- Subjects
0301 basic medicine ,Melanomas ,Disease status ,Cell signaling ,Biopsy ,Signal transduction ,Biochemistry ,0302 clinical medicine ,Medicine and Health Sciences ,Melanoma ,Regulation of gene expression ,Principal Component Analysis ,Multidisciplinary ,medicine.diagnostic_test ,Signaling cascades ,Prognosis ,Nucleic acids ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Metabolic Pathways ,Research Article ,Cell biology ,MAPK signaling cascades ,Science ,Surgical and Invasive Medical Procedures ,Ras Signaling ,03 medical and health sciences ,Diagnostic Medicine ,microRNA ,medicine ,Biomarkers, Tumor ,Genetics ,Cancer Detection and Diagnosis ,Humans ,RNA, Messenger ,Non-coding RNA ,Survival analysis ,Natural antisense transcripts ,Biology and life sciences ,business.industry ,Cancers and Neoplasms ,medicine.disease ,Survival Analysis ,Gene regulation ,Circulating biomarkers ,MicroRNAs ,030104 developmental biology ,Metabolism ,Cutaneous melanoma ,Cancer research ,RNA ,Gene expression ,business - Abstract
Background Histopathologic examination of melanocytic neoplasms can be challenging and subjective, with no specific circulating or tissue-based biomarkers currently available. Recently, a circulating 38-microRNA profile of melanoma (Mel38) was described. In this study, Mel38 expression and its impact on downstream mRNA regulation in solid tissue is examined. Methods Mel38 was applied to archival, clinically-annotated, solid-tissue genomic datasets representing benign naevi, primary and metastatic melanoma. Statistical analysis of the signature in relation to disease status, patient outcome and molecular pathways was performed. Results Mel38 is able to stratify genomic data from solid tissue biopsies on the basis of disease status and differences in melanoma-specific survival. Experimentally-verified messenger-RNA targets of Mel38 also exhibit prognostic expression patterns and represent key molecular pathways and events in melanoma development and progression. Conclusion The Mel38 microRNA profile may have diagnostic and prognostic utility in solid tissue as well as being a robust circulating biomarker of melanoma.
- Published
- 2018