Department of Zoology, Sri Venkateswara College, University of Delhi, Delhi, India.
Department of Zoology, Shivaji College, University of Delhi, Delhi, India.
Indian J Ophthalmol. 2024 Oct 1;72(10):1393-1403. doi: 10.4103/IJO.IJO_167_24. Epub 2024 Sep 27.
Eyelid sebaceous gland carcinoma (SGC) is an aggressive skin cancer characterized by a heightened risk of recurrence and metastasis. While surgical excision is the primary treatment, unraveling the molecular intricacies of SGC is imperative for advancing targeted therapeutic interventions and enhancing patient outcomes. This comprehensive review delves into the molecular landscape of eyelid SGC, emphasizing key genetic alterations, signaling pathways, epigenetic modifications, and potential therapeutic targets. Significant findings include aberrations in critical signaling pathways (β-catenin, lymphoid enhancer binding factor, hedgehog, epidermal growth factor receptor, P53, and P21WAF1) associated with SGC progression and poor prognosis. Notably, eyelid SGC manifests a distinctive mutational profile, lacking ultraviolet signature mutations in tumor protein 53 (TP53), indicating alternative mutagenic mechanisms. Next-generation sequencing identifies actionable mutations in genes such as phosphatase and tensin homolog (PTEN) and Erb-B2 receptor tyrosine kinase 2 (ERBB2), facilitating the emergence of personalized medicine approaches. Molecular chaperones, specifically X-linked inhibitor of apoptosis protein (XIAP) and BAG3, emerge as pivotal players in promoting tumor survival and proliferation. The review underscores the role of epithelial-mesenchymal transition, where regulators like E-cadherin, vimentin, and ZEB2 contribute to SGC aggressiveness. Epigenetic modifications, encompassing DNA methylation and microRNA dysregulation, further elucidate the molecular landscape. This review consolidates a comprehensive understanding of the molecular drivers of eyelid SGC, shedding light on potential therapeutic targets and providing a foundation for future investigations in diagnostic, prognostic, and personalized treatment strategies for this formidable malignancy.
眼睑皮脂腺癌 (SGC) 是一种侵袭性皮肤癌，其特点是复发和转移的风险较高。虽然手术切除是主要的治疗方法，但阐明 SGC 的分子复杂性对于推进靶向治疗干预和改善患者预后至关重要。本综述深入探讨了眼睑 SGC 的分子特征，强调了关键的遗传改变、信号通路、表观遗传修饰和潜在的治疗靶点。重要的发现包括与 SGC 进展和不良预后相关的关键信号通路（β-连环蛋白、淋巴增强结合因子、 hedgehog、表皮生长因子受体、P53 和 P21WAF1）的异常。值得注意的是，眼睑 SGC 表现出独特的突变谱，缺乏肿瘤蛋白 53（TP53）中的紫外线特征性突变，表明存在替代的诱变机制。下一代测序确定了磷酸酶和张力蛋白同源物 (PTEN) 和 Erb-B2 受体酪氨酸激酶 2 (ERBB2) 等基因中的可操作突变，促进了个性化医疗方法的出现。分子伴侣，特别是 X 连锁凋亡抑制蛋白 (XIAP) 和 BAG3，作为促进肿瘤存活和增殖的关键因素。该综述强调了上皮-间充质转化的作用，其中 E-钙黏蛋白、波形蛋白和 ZEB2 等调节剂有助于 SGC 的侵袭性。表观遗传修饰，包括 DNA 甲基化和 microRNA 失调，进一步阐明了分子特征。本综述综合了对眼睑 SGC 分子驱动因素的全面理解，为潜在的治疗靶点提供了启示，并为未来在诊断、预后和个性化治疗策略方面的研究提供了基础，以应对这一严重的恶性肿瘤。
