Table 3.
Molecular subtype characteristics in the discovery cohort
| Proliferative | |
| Up-regulated modules | 4, 5, 7 |
| Down-regulated modules | 6 |
| Clinical characteristics | Current smoking (86%), dysplastic biopsies (63%) |
| Biological characteristics | LUSC subytpes—classical and basal; TUB1A1, SCGB1A1 down regulated; KRT5, MKI67 up regulated |
| Pathways | Cell cycle: BUB1B/1/3, CHEK1/2, CDK1/2/4/6, E2F1/3/2/4, MCM4/3/5/6/7, TP53, RB1 |
| DNA repair: TP53, PARP1, RAD51, BRCA2, FANCA/D2/G/E/M/C, XRCC5/6, ERCC6 | |
| Oxidative phosphorylation and electron transport chain: ATP synthases, NADH-ubiquinone oxidoreductases, cytochrome C oxidases | |
| Transcription factors | E2F |
| Inflammatory | |
| Up-regulated modules | 1, 2, 7, 8 |
| Down-regulated modules | 4, 5, 6 |
| Clinical characteristics | Former smoking (59%), non-dysplastic biopsies (68%) |
| Biological characteristics | LUSC subytpes—secretory; TUB1A1, MUC5AC down regulated |
| Pathways | Extracellular matrix, focal adhesion, and integrin pathways: collagen, integrin, and laminin genes |
| Cytokine/chemokine: CCL2/14/19/21/28, CXCL12/14/5, CCR1/2/3/4/5, IL1B, IL11RA, IL17RB, IL1R1, IL3RA, EGF, IL15, CX3CR1, TGFB1/B2/B3, KIT | |
| Downregulation of oxidative phosphorylation, respiratory elecron transport, cell cycle | |
| Transcription factors | SRF |
| Secretory | |
| Up-regulated modules | 6, 8 |
| Down-regulated modules | 1, 2, 5, 7 |
| Clinical characteristics | Current smoking (63%), non-dysplastic biopsies (66%) |
| Biological characteristics | LUSC subytpes—secretory; CD45, MUC5AC, TUB1A1 up regulated; MKI67, KRT5 down regulated |
| Pathways | Down regulation of extracellular matrix, focal adhesion, integrin pathways |
| Transcription factors | Down regulation of E2F |
| Normal-like | |
| Up-regulated modules | 1, 6 |
| Down-regulated modules | 8, 9 |
| Clinical characteristics | Former smoking (65%), non-dysplastic biopsies (75%) |
| Biological characteristics | CD45, MUC5AC, MKI67 down regulated; SCGB1A1, KRT5, TUB1A1 up regulated |
| Pathways | Core extracellular matrix genes: collagen and laminin genes, WISP1/2 |
| Down regulation of innate and adaptive immunity: HLA genes, IRF1/4/7/8, TLR2/4/6/8/10, IKBKB | |
| Transcription factors | Down regulation of PEA3, IRF, NFKB |
For each molecular subtype, significant associations are reported between the molecular subtype and gene module GSVA scores, clinical characteristics, canonical cell type epithelial and white blood cell gene markers, biological pathways, and transcription factors. The modules are designated as up regulated or down regulated in each molecular subtype based on the direction of gene expression of the majority of genes in each module. Source data are provided as a Source Data file