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A comparative study of neuroendocrine heterogeneity in SCLC and NBL

Ling Cai, Ralph J. DeBerardinis, Yang Xie, John D. Minna, Guanghua Xiao
doi: https://doi.org/10.1101/2022.11.17.516959
Ling Cai
1Quantitative Biomedical Research Center, School of Public Health, UT Southwestern Medical Center, Dallas, TX 75390, USA
2Children’s Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA
3Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
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  • For correspondence: ling.cai@utsouthwestern.edu
Ralph J. DeBerardinis
2Children’s Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA
3Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
4Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Yang Xie
1Quantitative Biomedical Research Center, School of Public Health, UT Southwestern Medical Center, Dallas, TX 75390, USA
3Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
5Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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John D. Minna
3Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
6Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
7Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA
8Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Guanghua Xiao
1Quantitative Biomedical Research Center, School of Public Health, UT Southwestern Medical Center, Dallas, TX 75390, USA
3Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
5Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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  • For correspondence: ling.cai@utsouthwestern.edu
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Abstract

Lineage plasticity has long been documented in both small cell lung cancer (SCLC) and neuroblastoma (NBL), 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 NBL. We found NBL 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 NBL. We described many shared and unique NE score-associated features between SCLC and NBL, including dysregulation of Myc oncogenes, alterations in protein expression, metabolism, drug resistance, and selective gene dependencies. Our work establishes a reference for molecular changes and vulnerabilities associated with NE to non-NE transdifferentiation through mutual validation of SCLC and NBL samples.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted November 18, 2022.
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A comparative study of neuroendocrine heterogeneity in SCLC and NBL
Ling Cai, Ralph J. DeBerardinis, Yang Xie, John D. Minna, Guanghua Xiao
bioRxiv 2022.11.17.516959; doi: https://doi.org/10.1101/2022.11.17.516959
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A comparative study of neuroendocrine heterogeneity in SCLC and NBL
Ling Cai, Ralph J. DeBerardinis, Yang Xie, John D. Minna, Guanghua Xiao
bioRxiv 2022.11.17.516959; doi: https://doi.org/10.1101/2022.11.17.516959

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