Trefoil Family Factor Peptide 1—A New Biomarker in Liquid Biopsies of Retinoblastoma under Therapy

SIMPLE SUMMARY: Effective management of retinoblastoma (RB), a common childhood eye cancer, requires accurate diagnosis and monitoring during therapy. In this study, the liquid biopsy marker potential of the secreted trefoil family factor peptide 1 (TFF1), described as a biomarker of a more advanced RB subtype, was explored. TFF1 expression levels were investigated in aqueous humor (AH) of RB patients after enucleation and in RB patients undergoing intravitreal chemotherapy, and compared with TFF1 expression levels in RB patients’ blood serum. AH showed consistent TFF1 levels in a subgroup of RB patients, remarkably decreasing post-therapy in responsive patients. The blood serum of RB patients only displayed low-to-non-detectable and therapy-independent TFF1 levels. The study suggests TFF1 expression in AH is a reliable biomarker, aiding RB diagnosis and treatment assessment and highlights its potential for non-invasive RB therapy monitoring. ABSTRACT: 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.