Table 3.
CAF subpopulations identified in lung cancer
| CAF Subtype | Gene expression pattern | Ref. |
| Cluster 1 | • COL10A1 • Epithelial-mesenchymal transition-related genes • Expression of a high range of ECM proteins and TGF-β-associated genes • Upregulation of genes regulated by HOXB2 and FOXO1 (e.g., COL1A1, COL3A1 and COL6A1) | [152] |
| Cluster 2 | • COL4A1 • Highest expression of myofibroblast marker ACTA2 • High expression of myogenesis (for example, MEF2C, MYH11 or ITGA7 • NOTCH pathway-related genes • Angiogenesis-related genes • Pericytes subset expressing RGS5 (specific marker for pericytes) • Upregulation of MEF2C (myogenic transcription factor) and ELK3-regulated genes • Downregulation of FOXO1 and MSC (myogenic inhibitor) regulated genes | |
| Cluster 5 | • Lower myogenesis and high mTOR signature expression | |
| Cluster 6 (non-malignant fibroblasts) | • High levels of elastin • Low levels of collagens type I, III, V and VIII • Lack of collagen type VI expression | |
| Cluster 7 | • Lower myogenesis and high mTOR signature expression | |
| Subtype I | Function marker • HGFHigh, FGFHigh/Low, p-SMAD2Low Molecular marker • ADAMTS8, MMP3, MMP1, DLL4, … Suggested therapy: MET-plus-FGFR pathway blockade | [151] |
| Subtype II | Function marker • HGFLow, FGFHigh, p-SMAD2Low Molecular marker • WNT16, TNFSF4, KRT7, MALL, … Suggested therapy: FGFR pathway blockade | |
| Subtype III | Function marker • HGFLow, FGFLow, p-SMAD2High Molecular marker • RPS4Y1, EIF1AY, RPL10P9, HOXB9, … | |
| Branch 1 | Immunosuppressive CAFs • IGFBP6, IFITM3, LGALS3 Apoptosis, immune system, cytokine signal | [150] |
| Branch 2 | Antigen processing and presentation CAFs • UBE2T, TK1, CXCL12, KPNA2, and HMGB3 Cellular response to cytokine stimulus, antigen processing and presentation, and T cell receptor signaling pathway | |
| Branch 4 | Myofibroblastic CAFs • Enriched markers of extracellular organization ECM, cytokine secretion such as CCL2 and TGF-β, cell migration | |
| Branch 5 | Proliferative CAFs (the main identified population) • PRC1, AURKA Mitotic cell cycle process, cell division, cellular metabolic process |
CAF: Cancer-associated fibroblast; COL10A1: collagen type X alpha 1 chain; ECM: extracellular matrix; TGF-β: transforming growth factor beta; HOXB: homeobox B; FOXO1: forkhead box protein O1; COL1A1: collagen type I alpha 1 chain; COL3A1: collagen type III alpha 1 chain; COL6A1: collagen type VI alpha 1 chain; COL4A1: collagen type IV alpha 1 chain; ACTA2: actin alpha 2, smooth muscle; MEF2C: myocyte enhancer factor 2C; MYH11: myosin heavy chain 11; ITGA7: integrin subunit alpha 7; NOTCH: notch receptor 1; RGS5: regulator of G protein signaling 5; ELK3: ETS transcription factor ELK3; MSC: mTOR: mammalian target of rapamycin; HGF: hepatocyte growth factor; FGF: fibroblast growth factors; p-SMAD2: phosphorylated Sma- and Mad-related protein 2; ADAMTS8: a disintegrin and metalloproteinase with thrombospondin motifs 8; MMP: matrix metallopeptidase; DLL4: delta-like canonical Notch ligand 4; MET: mesenchymal–epithelial transformation; FGFR: fibroblast growth factor receptor; WNT16: Wnt family member 16; TNFSF4: TNF superfamily member 4; KRT7: keratin 7; MALL: mal, T cell differentiation protein-like; RPS4Y1: ribosomal protein S4 Y-linked 1; EIF1AY: eukaryotic translation initiation factor 1A Y-linked; RPL10P9: ribosomal protein L10; IGFBP6: insulin-like growth factor binding protein 6; IFITM3: interferon-induced transmembrane protein 3; LGALS3: galectin 3; UBE2T: ubiquitin-conjugating enzyme E2 T; TK1: thymidine kinase 1; CXCL: chemokine (C-X-C motif) ligand; KPNA2: karyopherin subunit alpha 2; HMGB3: high mobility group box 3; CCL: chemokine (CC motif) ligand; PRC1: protein regulator of cytokinesis 1; AURKA: Aurora kinase A.