Uveal melanoma (UVM) is a rare cancer that represents the second most common melanoma (after the cutaneous) and the most common primary intraocular malignancy in adults. Despite recent advances in the understanding of UVM pathogenesis, its prognosis remains unchanged, with half of patients dying because of liver metastasis. Erythropoietin-producing human hepatocellular receptors (EPHs) constitute the largest known family of tyrosine receptors, and, along with their ligands, EFNs, regulate key physiological processes and are implicated in cancer pathogenesis. In this study, we used open-access web bioinformatics platforms to explore and analyze big datasets provided by The Cancer Genome Atlas (TCGA) UVM cohort of patients. We profiled the genomic alterations present in a subset of UVM patients, highlighting a likely pathogenic deep deletion of EPHA7. Survival analysis showed that overexpression levels of EPHA4, EPHA5, EPHA8, EPHB2, and EFNB2 are significantly associated with poor overall survival. Additionally, high expression levels of EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2 correlate with reduced progression-free interval and disease-free survival. Finally, we identified the EPHs (EPHA2, EPHA4, EPHA8, and EPHB4) and EFNs (EFNA1, EFNA3, EFNA4, and EFNB2) that are significantly overexpressed in the aggressive epithelioid histological subtype and revealed that the majority of EPHs/EFNs are overexpressed in metastatic disease. In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are usually driven by activating mutations in KIT or PDGFRA. Although these alterations define the core molecular biology of GISTs and guide targeted therapy, they do not fully explain the variability observed in tumor behavior, recurrence risk, or response to tyrosine kinase inhibitors. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been increasingly studied as regulators of gene expression in GISTs. Recent evidence suggests that these molecules may influence KIT-centered signaling, autophagy, apoptosis, invasion, angiogenesis, and drug resistance. However, the strength of evidence differs considerably across individual ncRNAs, ranging from bioinformatic associations to functional validation in cell lines and in vivo models. This review summarizes current knowledge on ncRNA-mediated regulation in GIST biology, with emphasis on tumor progression, therapeutic resistance, and possible clinical relevance. Rather than treating ncRNAs as isolated biomarkers, they function as part of broader regulatory networks that interact with oncogenic signaling and epigenetic mechanisms. Although several ncRNAs appear promising as prognostic or predictive candidates, further validation in independent clinical cohorts is required before their integration into routine risk stratification or treatment decision-making.