Xu Mingpeng, Shi Hanhan, Shen Yongning, Yang Ludi, Luan Yu, Gu Xiang, Wen Xuyang, Zhou Chuandi, Jia Renbing, Ji Xunda, Zhao Peiquan, Han Minglei, Fan Jiayan, Chai Peiwei
Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Ophthalmol Sci. 2025 May 6;5(5):100820. doi: 10.1016/j.xops.2025.100820. eCollection 2025 Sep-Oct.
Cavitary retinoblastoma (CRB) represents a unique variant of retinoblastoma (RB) distinguished by the presence of translucent cavities, which are discernible through ophthalmoscopic examination. The present study was designed to elucidate the clinical implications and molecular signatures of CRB, thereby enhancing our understanding of this distinct subtype of RB.
A multicentric, nested case-control, retrospective cohort study combining spatial proteomic analysis.
In a longitudinal study encompassing 1360 RB patients, conducted over a 13-year timeframe from June 2008 to February 2022, cavitary spaces were detected within the tumors of 48 eyes of 46 patients. A control cohort of 180 eyes from 138 age-matched patients with non-CRB was selected, maintaining a 1:3 case-control ratio. Laser-captured spatial proteomic analysis was conducted to explore the pivotal molecular changes within this specific subtype. The silencing of MYCN was achieved using adeno-associated virus (AAV) 2-mediated gene therapy in patient-derived xenograft models.
Enucleation, chemotherapy, and focal therapy.
Overall survival and metastasis-free survival.
Cavitary RB was linked to enhanced metastasis-free survival ( = 0.007) and overall survival ( = 0.03), as well as an increased proportion of well-differentiated status ( < 0.001) and a reduced incidence of vitreous seeding ( = 0.02). Spatial proteomic analysis, immunofluorescence, and immunohistopathology revealed a lower MYCN expression in CRB than in non-CRB. Silencing MYCN in patient-derived xenografts using AAV recapitulated these phenotypes of CRB, including the formation of translucent cavities and the emergence of cone-like rosettes.
This study establishes a novel genetic-phenotypic association, revealing that diminished MYCN expression induces the formation of translucent cavities. This phenotype is indicative of a less aggressive, well-differentiated CRB subtype with a more favorable prognosis.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
空洞性视网膜母细胞瘤（CRB）是视网膜母细胞瘤（RB）的一种独特变体，其特征是存在可通过检眼镜检查识别的半透明空洞。本研究旨在阐明CRB的临床意义和分子特征，从而加深我们对这种RB独特亚型的理解。
一项多中心、嵌套病例对照、回顾性队列研究，并结合空间蛋白质组学分析。
在一项从2008年6月至2022年2月的13年时间跨度内纳入1360例RB患者的纵向研究中，在46例患者的48只眼中检测到肿瘤内有空洞。从138例年龄匹配的非CRB患者中选取180只眼作为对照队列，保持1:3的病例对照比例。进行激光捕获空间蛋白质组学分析，以探索这一特定亚型内的关键分子变化。在患者来源的异种移植模型中，使用腺相关病毒（AAV）2介导的基因疗法实现MYCN沉默。
眼球摘除术、化疗和局部治疗。
总生存期和无转移生存期。
空洞性RB与无转移生存期延长（P = 0.007）、总生存期延长（P = 0.03）、高分化状态比例增加（P < 0.001）以及玻璃体种植发生率降低（P = 0.02）相关。空间蛋白质组学分析、免疫荧光和免疫组织病理学显示，CRB中MYCN表达低于非CRB。使用AAV在患者来源的异种移植中沉默MYCN可重现CRB的这些表型，包括半透明空洞的形成和锥状玫瑰花结的出现。
本研究建立了一种新的基因-表型关联，揭示MYCN表达降低诱导半透明空洞的形成。这种表型表明CRB亚型侵袭性较低、分化良好，预后更有利。
作者对本文讨论的任何材料均无所有权或商业利益。
