Melaseq has been carefully developed and validated to support advancements in melanoma diagnostics.
Our research has been featured in respected scientific journals, including the British Journal of Cancer, PLOS ONE, Melanoma Research, Biomarkers in Medicine, and the British Journal of Dermatology.
Background: New diagnostic tools are needed to improve the diagnosis and risk stratification of cutaneous melanoma. Disease-specific microRNA signatures have been previously described via NanoString profiling of solid biopsy tissue and plasma. This study validated these signatures via next-generation sequencing technology and compared their performance against clinical metrics and other published melanoma signatures.
Methods: RNA from 64 plasma and 60 FFPE biopsy samples from individuals with invasive melanoma or related benign/control phenotypes was extracted and enriched for microRNA. RNA sequencing was performed to compute MEL38/MEL12 signature scores. The results were evaluated with published NanoString and RNA sequencing datasets, comprising 548 solid tissue samples and 217 plasma samples, to predict disease status and patient outcome.
Results: The MEL38 diagnostic signature classifies patients into discrete diagnostic groups via RNA sequencing in either solid tissue or plasma (P < 0.001). In solid tissue, the prognostic MEL12 signature stratifies patients into low-, intermediate- and high-risk groups, independent of clinical covariates. The hazard ratios for 10-year overall survival, based on observed survival intervals, were 2.2 (MEL12 high-risk vs low-risk, P < 0.001) and 1.8 (intermediate-risk vs low-risk, P < 0.001), outperforming other published prognostic models. MEL12 also exhibited prognostic significance in the plasma of 42 patients with invasive disease.
Conclusions: The MEL38 and MEL12 signatures can be assessed in either solid tissue or plasma using RNA-seq and are strong predictors of disease state and patient outcome. Compared with other genomic methods, MEL12 was shown to be the strongest predictor of poor prognosis. MicroRNA expression profiling offers objective, accurate genomic information about a patient’s likelihood of invasive melanoma and prognosis.
Citation: https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-024-02028-w
Background: Noninvasive molecular biomarkers are needed to improve the early, accurate, and precise diagnosis of invasive cutaneous melanoma.
Objectives: To independently validate a previously identified circulating microRNA signature of melanoma (MEL38), and, secondly, to develop a complementary microRNA signature, optimized for prognostication.
Patients and Methods: MicroRNA expression profiling was performed on plasma samples from a multicentre observational case–control study, involving patients with primary or metastatic melanoma, melanoma in situ, nonmelanoma skin cancer, or benign naevi…
Results: Circulating microRNA profiles of 372 patients with invasive melanoma and 210 control individuals were generated. The average age of all participants was 59 years; 49% were male. A MEL38 score > 5.5 indicated the presence of invasive melanoma…
Conclusions: The circulating MEL38 signature may assist in diagnosing patients with invasive melanoma vs. other conditions associated with a lower – or negligible – risk of mortality…
Citation: https://academic.oup.com/bjd/article/189/3/292/7152924
Aim: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers…
Patients & Methods: Nanostring digital gene expression assessment of the MEL38 signature was performed on 308 formalin-fixed paraffin-embedded biopsies of nevi, melanoma in situ and invasive melanoma…
Results: The MEL38 score can stratify higher-risk melanomas (MPATH-Dx class V or more advanced) from lower-risk skin lesions (class I–IV) with an area under the curve of 0.97 (p < 0.001)…
Conclusion: Melanoma-specific circulating miRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin…
Citation: https://www.futuremedicine.com/doi/10.2217/bmm-2021-0289
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.
Aim: In this study, the expression of Mel38 in solid tissue is examined in the context of disease state, patient outcome, and messenger-RNA regulation.
Methods: Mel38 was applied to newly-created and archival, clinically-annotated, solid-tissue genomic datasets representing benign naevi, primary and metastatic melanoma. Univariate and multivariate statistical analyses of the signature in relation to disease status, patient outcome, and molecular pathways were performed.
Results: Mel38 was able to stratify genomic data from solid tissue biopsies on the basis of disease state and identify patient subgroups with significant differences in melanoma-specific survival. The 278 experimentally-verified messenger-RNA targets of Mel38 also exhibit significant prognostic expression patterns. Pathway and functional analysis showed that Mel38 regulates a significant subset of the Melanoma KEGG pathway as well as key gene categories required for melanoma development and progression.
Discussion: The Mel38 microRNA profile may have diagnostic and prognostic utility in solid tissue, as well as being a robust circulating biomarker of melanoma.
Link: https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(18)31011-0/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.
Citation: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211504
Effective management of melanoma depends heavily on early diagnosis. When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection. However, when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10–25%, respectively, due to limited efficacy of current treatment options. This presents a pressing need to identify biomarkers that can detect patients at high risk of recurrence and progression to metastatic disease, which will allow for early intervention and survival benefit.
Accumulating evidence over the past few decades has highlighted the potential use of circulating molecular biomarkers for melanoma diagnosis and prognosis, including lactate dehydrogenase (LDH), S100 calcium-binding protein B (S100B), and circulating tumor DNA (ctDNA) fragments. Since 2010, circulating microRNAs (miRNAs) have been increasingly recognised as more robust non-invasive biomarkers for melanoma due to their structural stability under the harsh conditions of the blood and different conditions of sample processing and isolation. Several pre-analytical and analytical variables challenge the accurate quantification of relative miRNA levels between serum samples or plasma samples, leading to conflicting findings between studies on circulating miRNA biomarkers for melanoma.
“This highlights the benefit of using a collection of miRNAs as a signature. If used individually, many of the miRNAs in MEL38 cannot be considered as independent biomarkers, however, when used in combination, they appear to provide a sensitive and specific tool.”
Background: In Australia, more money is spent on skin cancer than any other malignancy. Despite this, the mortality rate of melanoma, the deadliest form, has steadily increased over the past 50 years. Diagnostic imprecision and a lack of complementary molecular biomarkers are partially responsible for this lack of progress.
Methods: Whole-microRNAome profiling was performed on plasma samples from 32 patients with histologically confirmed melanoma and 16 normal controls. A classification algorithm was trained on these data and independently validated on multiple previously published microRNA data sets, representing (i) melanoma patient- and normal-blood, (ii) melanoma and nevi biopsy tissue, and (iii) cell lines and purified exosomes.
Results: Thirty-eight circulating microRNAs had biologically and statistically significant differences between melanoma and normal plasma samples (MEL38). A support vector machine algorithm, trained on these markers, showed strong independent classification accuracy (AUC 0.79–0.94). A majority of MEL38 genes have been previously associated with melanoma and are known regulators of angiogenesis, metastasis, tumour suppression, and treatment resistance.
Conclusions: MEL38 exhibits disease state specificity and robustness to platform and specimen-type variation. It has potential to become an objective diagnostic biomarker and improve the precision and accuracy of melanoma detection and monitoring.
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