Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data, we applied non-negative matrix factorization, which identified four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed signature (SCLC-A, N, P and I, respectively). The presence of these subtypes were then validated in tumor gene expression data from the IMpower133 clinical trial.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Samples
EGAD00001006926	This dataset contains subtype assignments for 271 tumor samples profiled by RNA-seq.	271
EGAD00001006927	This dataset contains log2(TPM + 1) for 271 tumor samples profiled by RNA-seq for the entire transcriptome.	271
EGAD00001006928	This dataset contains log2(TPM + 1) for 271 tumor samples profiled by RNA-seq for the subset of genes used for validation of the NMF cluster assignments.	271

Publications	Citations
Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, Nabet BY, Fujimoto J, Solis LM, Lu W, Xi Y, Cardnell RJ, Wang Q, Fabbri G, Cargill KR, Vokes NI, Ramkumar K, Zhang B, Della Corte CM, Robson P, Swisher SG, Roth JA, Glisson BS, Shames DS, Wistuba II, Wang J, Quaranta V, Minna J, Heymach JV, Byers LA. Cancer Cell 39: 2021 346-360.e7	359
Transcriptional Profiling Reveals Mesenchymal Subtypes of Small Cell Lung Cancer with Activation of the Epithelial-to-Mesenchymal Transition and Worse Clinical Outcomes. Cho HJ, Hong SA, Ryu D, Hong SH, Kim TM. Cancers (Basel) 14: 2022 5600	1
Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes. Heeke S, Gay CM, Estecio MR, Tran H, Morris BB, Zhang B, Tang X, Raso MG, Rocha P, Lai S, Arriola E, Hofman P, Hofman V, Kopparapu P, Lovly CM, Concannon K, De Sousa LG, Lewis WE, Kondo K, Hu X, Tanimoto A, Vokes NI, Nilsson MB, Stewart A, Jansen M, Horváth I, Gaga M, Panagoulias V, Raviv Y, Frumkin D, Wasserstrom A, Shuali A, Schnabel CA, Xi Y, Diao L, Wang Q, Zhang J, Van Loo P, Wang J, Wistuba II, Byers LA, Heymach JV. Cancer Cell 42: 2024 225-237.e5	14