A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma

Abstract

Abstract Lineage plasticity has long been documented in both small cell lung cancer (SCLC) and neuroblastoma, two clinically distinct neuroendocrine (NE) cancers. In this study, we quantified the NE features of cancer as NE scores and performed a systematic comparison of SCLC and neuroblastoma. We found neuroblastoma and SCLC cell lines have highly similar molecular profiles and shared therapeutic sensitivity. In addition, NE heterogeneity was observed at both the inter- and intra-cell line levels. Surprisingly, we did not find a significant association between NE scores and overall survival in SCLC or neuroblastoma. We described many shared and unique NE score–associated features between SCLC and neuroblastoma, including dysregulation of Myc oncogenes, alterations in protein expression, metabolism, drug resistance, and selective gene dependencies. Implications: Our work establishes a reference for molecular changes and vulnerabilities associated with NE to non-NE transdifferentiation through mutual validation of SCLC and neuroblastoma samples.