Abstract
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. In this review, we provide a critical summary of the circulating miRNA biomarkers for melanoma published to date.
Highlights
Melanoma is an aggressive cancer derived from melanocytes found predominantly in the skin, and in the eyes, ears, gastrointestinal tract, and oral and genital mucosal membranes.The global incidence of melanoma has increased dramatically over the past few decades
This study demonstrated that miR-210 levels were higher in the serum of stage IV melanoma patients relative to stage III melanoma patients, they were unable to verify this difference in the validation study
It has been demonstrated that SYBR-Green based quantitative reverse transcription polymerase chain reaction (qRT-polymerase chain reaction (PCR)) is less sensitive and specific compared to TaqMan qRT-PCR, yielding higher Cqs and broader variation within patient groups due to more stochastic qPCR amplification [74]. This can result in significant differences in miRNA expression between patient groups that are otherwise undetected when using TaqMan qRT-PCR. In support of these findings, we demonstrated that TaqMan microRNA qRT-PCR assays have higher detection sensitivity and specificity compared to SYBR-Green based microRNA qRT-PCR assays (Figure 2b and Supplementary data)
Summary
Melanoma is an aggressive cancer derived from melanocytes found predominantly in the skin, and in the eyes, ears, gastrointestinal tract, and oral and genital mucosal membranes. The global incidence of melanoma has increased dramatically over the past few decades. In the UK alone, melanoma incidence rates have increased by a staggering 128% since the early 1990s, rendering melanoma the UK’s fifth most common cancer with around 15,906 new cases each year. While melanoma accounts for only 4% of new skin cancer cases in the UK each year, it is the cause of more than 95% of skin cancer-related deaths, and is considered the most common fatal malignancy of young adults [1]. When detected in the early non-metastatic stages I and II, melanoma has a 5-year survival rate of ~100% and 80–90%, respectively, as thin localized tumors are highly curable by surgical resection.
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