Busch Maike Anna, Haase André, Alefeld Emily, Biewald Eva, Jabbarli Leyla, Dünker Nicole
Institute of Anatomy II, Department of Neuroanatomy, Medical Faculty, Center for Translational Neuro and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany.
Department of Ophthalmology, Children's Hospital, University of Duisburg-Essen, 45147 Essen, Germany.
Cancers (Basel). 2023 Oct 2;15(19):4828. doi: 10.3390/cancers15194828.
Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1-secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC-therapy-responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients' blood serum displayed low-to-undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared with blood serum, AH represents the more reliable source of TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimally invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.
视网膜母细胞瘤(RB)是最常见的儿童眼癌,其有效管理依赖于可靠的监测和诊断。在这种情况下,一个有前景的候选物是分泌型三叶因子家族肽1(TFF1),它最近被发现是视网膜母细胞瘤更晚期亚型患者中有前景的新生物标志物。本研究调查了摘除眼球房水中TFF1的表达,并比较了接受玻璃体内化疗(IVC)的RB患者房水和相应血清样本中的TFF1水平。在房水中始终可检测到TFF1,证实了其作为生物标志物的潜力。至关重要的是,我们的数据证实肿瘤块内分泌TFF1的细胞起源于RB肿瘤细胞,而非周围的基质细胞。IVC治疗有反应的患者治疗后TFF1水平显著降低。相比之下,RB患者的血清即使经过样本浓缩后TFF1水平仍较低甚至无法检测到,且未观察到治疗依赖性变化。我们的研究结果表明,与血清相比,若用于RB患者的液体活检RB标志物分析,房水是更可靠的TFF1来源。因此,分析RB患者房水中的TFF1可能为监测RB治疗效果提供一种微创工具,表明其对有效治疗方案的重要性。