Abstract
Integrative analysis of multi-omics data reveals the heterogeneity and signatures of immune therapy for small cell lung cancer.
Highlights
Small cell lung cancer (SCLC) is one of the deadliest cancers marked with fast proliferation and early metastasis
We identified four dominant subtypes with a robust clustering approach based on gene modules, two of which correspond well with the classic (ASCL1-high, NEUROD1-low) and variant (ASCL1-low, NEUROD1-high) subtypes
The remaining subtype represents a novel variant subtype characterized with lower expression of both ASCL1 and NEUROD1, higher expression of NOTCH1/2, showing increased immunogenic and consequent immunosuppressive features, which is defined as an immune subtype
Summary
Small cell lung cancer (SCLC) is one of the deadliest cancers marked with fast proliferation and early metastasis. Two subtypes of SCLC have been previously recognized for decades: the classic subtype and the variant subtype[1, 7, 8, 9]. The lineage-specific transcription factor, ASCL1, is associated with the NE property and overexpressed in the classical subtype[10]. Down-regulation of ASCL1 expression in the variant subtype may contribute to its loss of NE property. Another transcription factor, NEUROD1, is reported to be important in maintenance of the variant subtype[10, 11]. Distinct four SCLC molecular subtypes have been proposed based on the expression of ASCL1, NEUROD1, POU2F3 and YAP112. The network-based subtyping with a larger dataset is expected to provide reliable subtypes of SCLC patients, in contrast to the four subtypes obtained by a traditional expression-based subtyping with a relatively small dataset[12]
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