Current Trends in Circulating Biomarkers for Melanoma Detection

Abstract

Melanomas have increased in global incidence and are the leading cause of skin cancer deaths. Whilst the majority of early-stage, non-metastatic melanomas can be cured with surgical excision alone, ~5% of patients with early melanomas will experience recurrence following a variable disease-free interval and progression to metastatic melanoma and ultimately death. This is likely because of primary tumor heterogeneity and progressive clonal divergency resulting in the growth of more aggressive tumor populations. Liquid biomarkers have the advantage of real-time, non-invasive longitudinal monitoring of tumor burden and heterogeneity over tissue markers. Currently, the only serological marker used in the staging and monitoring of melanoma is serum lactate dehydrogenase, which is not sufficiently specific or sensitive, and is not used routinely in all centers. An ideal melanoma biomarker would be used to identify patients who are at high-risk of primary melanoma, screen for relapse, detect early-stage melanoma, provide treatment outcomes to personalize systemic treatment, follow tumor heterogeneity, provide prognostic data before, during and after treatment, and monitor response to treatment. This review provides a summary of the current research in this field with a specific focus on circulating tumor cells, circulating tumor DNA, microRNA, and extracellular vesicles which may serve to suit these goals.

pTERT C250T mutation: a potential biomarker of poor prognosis in metastatic melanoma

“…The inability to detect pTERT mutations in the plasma of discordant cases (7/11), can be explained by the low amounts of ctDNA available due to the variable tumor shedding into the bloodstream. The presence of different types of pTERT mutations between plasma and tissue has been observed in the remaining discordant cases, which can be explained by tumor heterogeneity in tissue samples 29,30 . Even so, considering that plasma detection rates of pTERT mutations are lower than those of other driver genes such as BRAF (> 80%) [31][32][33] , larger cohort studies would be needed to con rm its usefulness as a potential biomarker in melanoma.…”

Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach

“…Circulating tumor miRNAs (ct-mirRNAs) are more stable compared with other extracellular RNAs: they are complexed with proteins or lipoproteins such as Argonaute 2 (AGO2), or packaged inside EVs which protect them against RNase activity [ 114 ]. Despite high stability in blood, their low concentration and lack of consistent processes for collection make the pre-analytical phase of ct-miRNAs detection a critical step to minimize analytical variabilities [ 115 ].…”

“…Many ct-miRNAs are found to be up- or down-regulated in the blood of cancer patients [ 122 ]. Up-regulation of miR-221, involved in cell cycle regulation and proliferation, has been observed in a large number of tumors such as glioblastoma [ 123 ], lung cancer [ 124 ], breast cancer [ 125 ], thyroid papillary carcinoma [ 126 ], hepatocellular carcinoma [ 127 ], and melanoma [ 114 ]. Down-regulation of miR-192, miR-194, and miR-215 prevent apoptosis in multiple myeloma [ 128 ].…”

Extracellular vesicles and melanoma: New perspectives on tumor microenvironment and metastasis

“…Circulating miRNA are also promising biomarkers and have also shown their association with melanoma progression ( Huang et al, 2022 ). In particular, MV-associated let-7g-5p and miR-497-5p have been suggested as putative predictive markers in response to MAPK inhibitors in melanoma ( Svedman et al, 2018 ).…”