LAUSR

Recently we showed that Retinal degeneration protein 3 (RD3) is constitutively expressed in healthy adult and fetal tissues beyond retina and, its gradient expression from high to low in ganglioneuroma, ganglioneuroblastoma and neuroblastoma (NB). Crucially, our sequential in vitro and in vivo studies identified that RD3 regulates NB progression and metastasis, and its loss prompts the evolution of therapy defying progressive disease (PD). Here we investigated the prognostic significance of RD3 in NB, its predictive benefit and, its association to clinical outcomes. RNA-Seq data mining (4 independent study cohorts, total n = 1013) indicated that high RD3 can predict good NB prognosis. RD3 expression (immunohistochemistry) gauged in our NB patient cohort (n = 100) showed a positive correlation with longer overall survival (OS, P = 1.0E-04) and relapse-free survival (RFS, P = 2.1E-02). Similarly, high RD3 correlated with longer OS (P = 1.2E-03) and RFS (P = 2.1-02) in children presented with high-risk NB (HR-NB), irrespective of MYCN amplification status (MYCN amplified, P = 1.4E-02; non-amplified, P = 5.5E-03) and patient age (<2Y age, P = 2.8E-02; >2Y age, P = 1.0E-04) groups. Significantly, we observed a gradient loss of RD3 with NB progression, from stage 1 through stage 4 disease. Consistently, RD3 loss was substantial in metastatic disease when compared to the primary neuroblastomas, and this loss associated with poor OS in patients presented with metastatic disease (P = 4.0E-02). More importantly, RD3 is significantly lost in therapy resistant progressive NB and corroborated significantly (P = 9.5E-03) with the poor progression free survival. Multivariate analysis identified RD3 as an independent (P = 4.4E-02) prognostic factor for NB. These results demonstrate that RD3-loss can forecast poor prognosis in NB, and further imply that assessing RD3 loss could serve as the good predictor for therapy response and/or PD evolution. Together, these data identify a novel prognostic and predictive factor for neuroblastoma. Funding: This work was partially or in full, funded by Oklahoma Center for the Advancement of Science and Technology, OCAST-HR19-045; National Institutes of Health, NIH-P20GM103639 and Department of Defense DoD-CA210339 Citation Format: Dinesh Babu Somasundaram, Zhongxin Yu, Ashley Baker, Natarajan Aravindan. Novel prognostic and predictive biomarker for neuroblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4517.