Abstract 2800: Unraveling long non-coding RNA dynamics in uveal melanoma: Insights into pathogenesis, biomarkers, and targeted therapies

Abstract Uveal melanoma (UM), a rare yet aggressive intraocular cancer with an estimated 5 cases per million people annually, presents a high metastatic risk and poor prognosis, highlighting an immeasurable need for novel diagnostic and therapeutic strategies. Not only is UM characterized by complex genetic and epigenetic aberrations, but it is also prone to deregulation of non-coding RNAs that could be used as therapeutic targets of diagnostic markers. In this study, we analyzed whole exome sequencing data from tumor and control samples of patients diagnosed with both uveal and cutaneous melanoma, focusing on a patient with a germline mutation in MBD4. Our framework, made up to work with long non-coding RNAs (lncRNAs), aims to flesh out these molecules' novel roles in disease etiology and progression. We identified several lncRNAs significantly associated with UM progression and computationally validated them in conjunction with microenvironmental factors in existing literature. LncRNAs are instructive in maintaining cellular homeostasis and, when deregulated, contribute to oncogenesis. Our results implied that the interaction between lncRNAs and other non-coding RNAs might be one of the most relevant mechanisms influencing UM pathogenesis. More interestingly, microenvironmental factors and lncRNA interplay are crucial in disease progression. The clinical relevance of our findings was tested using radiation treatment to evaluate potential therapeutic implications. Over and above that, we assessed the potential of lncRNAs as biomarkers and therapeutic targets in personalized medicine for UM patients to address ineffective treatments. The new lncRNA panels could serve as a new avenue for targeted therapy. With an in-depth understanding of the descent of molecular alterations and how lncRNAs interact within the tumor microenvironment, we can better size up potential strategies to cast off the challenges UM poses. Our work provides instructive insights into lncRNAs underpinnings of UM, emphasizing the significance of lncRNAs in tumor biology and their interactions within the microenvironment. We believe our findings will lay the groundwork for future therapeutic strategies and underscore the necessity for continued research to unravel the complex mechanisms in UM pathogenesis. Citation Format: Vasileios Alevizos, Nikitas Gerolimos, Sabrina Edralin, Clark Xu, Akebu Simasiku, Georgios Priniotakis, George A. Papakostas, Zongliang Yue. Unraveling long non-coding RNA dynamics in uveal melanoma: Insights into pathogenesis, biomarkers, and targeted therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2800.