The purpose of this article is to provide a literature review of the epigenetic understanding of conjunctival melanoma (CM), with a primary focus on current gaps in knowledge and future directions in research. CM is a rare aggressive cancer that predominantly affects older adults. Local recurrences and distant metastases commonly occur in CM patients; however, their prediction and management remain challenging. Hence, there is currently an unmet need for useful biomarkers and more effective treatments to improve the clinical outcomes of these patients. Like other cancers, CM occurrence and prognosis are believed to be influenced by multiple genetic and epigenetic factors that contribute to tumor development/progression/recurrence/spread, immune evasion, and primary/acquired resistance to therapies. Epigenetic alterations may involve changes in chromatin conformation/accessibility, post-translational histone modifications or the use of histone variants, changes in DNA methylation, alterations in levels/functions of short (small) or long non-coding RNAs (ncRNAs), or RNA modifications. While recent years have witnessed a rapid increase in available epigenetic technologies and epigenetic modulation-based treatment options, which has enabled the development/implementation of various epi-drugs in the cancer field, the epigenetic understanding of CM remains limited due to a relatively small number of epigenetic studies published to date. These studies primarily investigated DNA methylation, ncRNA (e.g., miRNA or circRNA) expression, or RNA methylation. While these initial epigenetic investigations have revealed some potential biomarkers and/or therapeutic targets, they had various limitations, and their findings warrant replication in independent and larger studies/samples. In summary, an in-depth understanding of CM epigenetics remains largely incomplete but essential for advancing our molecular knowledge and improving clinical management/outcomes of this aggressive disease.
本文旨在综述结膜黑色素瘤（CM）的表观遗传学研究进展，重点探讨当前认知空白及未来研究方向。CM是一种罕见的高度侵袭性肿瘤，好发于老年人群。局部复发与远处转移在CM患者中较为常见，但其预测与临床管理仍面临挑战。因此，当前亟需有效的生物标志物和更优化的治疗方案以改善患者临床结局。与其他恶性肿瘤相似，CM的发生发展与预后被认为受到多种遗传及表观遗传因素影响，这些因素共同参与肿瘤发生/进展/复发/转移、免疫逃逸以及原发性/获得性治疗抵抗等过程。表观遗传改变可能涉及染色质构象/可及性变化、组蛋白翻译后修饰或组蛋白变体替换、DNA甲基化改变、短链（小分子）或长链非编码RNA（ncRNA）水平/功能变化以及RNA修饰等机制。尽管近年来表观遗传技术及基于表观调控的治疗方案快速发展，推动多种表观药物在肿瘤领域的开发与应用，但针对CM的表观遗传学研究仍较为有限，主要受限于目前已发表的相关研究数量较少。现有研究主要聚焦DNA甲基化、ncRNA（如miRNA或circRNA）表达或RNA甲基化等领域。这些初步探索虽揭示了部分潜在生物标志物和/或治疗靶点，但其研究存在诸多局限性，相关发现仍需在更大规模独立样本中验证。总之，对CM表观遗传机制的深入理解尚存不足，但这对深化疾病分子认知、改善临床治疗策略与患者预后具有至关重要的意义。
Epigenetics of Conjunctival Melanoma: Current Knowledge and Future Directions
肿瘤(癌症)患者之家