Abstract 2349: SAP30, a novel drug response specific transcription factor in high-risk neuroblastoma

Abstract

Abstract Neuroblastoma is the most devastating extracranial solid malignancy in children. Despite an intense treatment regimen, the prognosis for high-risk neuroblastoma patients remains poor, with less than 40% survival. So far, MYCN status/amplification is considered the most prognostic factor but corresponds to only 25% of neuroblastoma patients. Therefore, it is essential to identify a better prognosis and prediction marker of therapy response in neuroblastoma patients. The identification of master regulators with good prognostic and drug response abilities are not successful due to the complexity and lack of data-driven bioinformatic workflows. We applied robust bioinformatic data mining tools such as Weighted Gene Co-expression Network Analysis, cisTarget, and Single-Cell rEgulatory Network Inference and Clustering on three neuroblastoma patient datasets (n=1252). We found Sin3A Associated Protein 30 (Sap30), a driver transcription factor positively associated with high-risk, progression, stage 4, and poor survival in high-risk neuroblastoma patient cohorts. Tumors of high-risk neuroblastoma patients and relapse-specific patient-derived xenografts showed higher Sap30 levels. The Genomics of Drug Sensitivity in Cancer, The Cancer Cell Line Encyclopedia, and CRISPR-Cas9 screens indicated that Sap30 essentiality is associated with Cisplatin resistance and further showed higher levels in Cisplatin resistant patient-derived xenograft tumor cell lines. The silencing of Sap30 in cells reduced cell growth, induced cell death, mitochondrial membrane potential loss in vitro, and reduced tumorigenicity in vivo. Altogether, these results indicate that Sap30 is a novel prognostic and Cisplatin resistant marker and thus a potential drug target in high-risk neuroblastoma patients. Citation Format: Philip Prathipati, Anup S. Pathania, Nagendra K. Chaturvedi, Subash C. Gupta, Siddappa N. Byrareddy, Don W. Coulter, Kishore B. Challagundla. SAP30, a novel drug response specific transcription factor in high-risk neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2349.