Molecular subtyping of small-cell lung cancer in clinical practice: Primary tumor-lymph node concordance, intratumoral heterogeneity, and genomic context in a Chinese cohort.

Subtypes were dominated by ASCL1- and NEUROD1-driven programs, with one-third of tumors exhibiting mixed A/N expression.

NEUROD1 correlated strongly with NFIB and INSM1, and NEUROD1 expression was high in paired regional lymph node metastases, supporting migratory or plastic phenotype associations.

CASP10 was markedly downregulated in tumors relative to that in normal lung or lymphoid tissues.

Genomic profiling confirmed canonical TP53/RB1 dual inactivation pattern alongside recurrent alterations in NOTCH1, PIK3CA, CREBBP, and KMT2D.