Future perspectives of uveal melanoma blood based biomarkers

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy affecting adults. Despite successful local treatment of the primary tumour, metastatic disease develops in up to 50% of patients. Metastatic UM carries a particularly poor prognosis, with no effective therapeutic option available to date. Genetic studies of UM have demonstrated that cytogenetic features, including gene expression, somatic copy number alterations and specific gene mutations can allow more accurate assessment of metastatic risk. Pre-emptive therapies to avert metastasis are being tested in clinical trials in patients with high-risk UM. However, current prognostic methods require an intraocular tumour biopsy, which is a highly invasive procedure carrying a risk of vision-threatening complications and is limited by sampling variability. Recently, a new diagnostic concept known as “liquid biopsy” has emerged, heralding a substantial potential for minimally invasive genetic characterisation of tumours. Here, we examine the current evidence supporting the potential of blood circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), microRNA (miRNA) and exosomes as biomarkers for UM. In particular, we discuss the potential of these biomarkers to aid clinical decision making throughout the management of UM patients.

Uveal Melanoma

“…CtDNA and cmiRNA can also be extracted from blood and detected by PCR. 21 Perhaps the most sensitive marker, CtDNA was detected in the blood of 100% of patients with uveal melanoma, but also detected in 50% of patients with ocular nevi. 29 CmiRNA was used to differentiate benign uveal nevi from uveal melanoma with 93% sensitivity and 100% specificity.…”

“…CTCs can be extracted from blood, isolated using immunomagnetic beads, and quantified using RT-PCR. 21 Studies using gp100 and CD63 for isolation of CTCs have achieved as much as a 94% detection rate for uveal melanoma. 27 In addition, CTCs are not found in patients with ocular nevi.…”

“…Figure 1. Macroscopic images of choroid(A), ciliary body(B), and iris melanoma(C) Figures taken from Beasley et al21 …”

Integration of Bulk RNA Sequencing and Single-Cell RNA Sequencing to Reveal Uveal Melanoma Tumor Heterogeneity and Cells Related to Survival

“…The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy ( 5 ). Even with successful local treatment of primary tumors, more than 50% of UM patients will develop metastatic diseases ( 6 , 7 ). For patients, there is no effective treatment option so far.…”

Sclerostin Suppression Facilitates Uveal Melanoma Progression Through Activating Wnt/β-Catenin Signaling Via Binding to Membrane Receptors LRP5/LRP6

“…Uveal melanoma (UM) represents the most frequent primary intraocular tumor in adults as well as the second most frequent form of melanoma (1). It originates from the pigmented uveal tract, composed of choroid (~85%), ciliary body (5-8%), and iris (3-5%) (2,3). In accordance with the WHO classification of histological types in 1980, UM is categorized as spindle cell type with low malignancy, epithelioid cell type with high malignancy, mixed cell type, and other types (4).…”