Table 1.
Molecular Pancreatic Ductal Adenocarcinoma (PDAC) signatures.
| Author | Type of Study | Type and Number of PDAC Samples | Dysregulated Pathways and Mutations | Outcome |
|---|---|---|---|---|
| Collison et al. [31] | Transcriptional | 1. Clinical samples microarray datasets Microdissected (n = 27) GSE15471 (n = 36) GSE11838 (n = 107) GSE16515 (n = 52) E-MEXP-950 (n = 50) 2. Validation: Mouse cell lines (n = 15) Human cell lines (n = 19) |
Classical: (↑) Adhesion-associated genes (GATA6). More K-RAS-dependent | Good |
| Quasi-mesenchymal: (↑) Mesenchymal associated genes | Bad | |||
| Exocrine: (↑) Digestive exocrine enzyme genes | ||||
| Moffit et al. [33] | Transcriptional | 1. Microarray data Primary tumour (n = 145) Metastatic tumour (n = 61) Cell lines (n = 17) Pancreas normal samples (n = 46) Distant site adjacent samples (n = 88) 2. Validation Primary tumours (n = 15) PDXs (n = 37) Cell lines (n = 3) CAF lines (n = 6) |
Classical: Classical Collison ((↑) adhesion-associated genes (GATA6)) and SMAD4 | Good |
| Basal: (↑) Genes also highly expressed in basal tumours in bladder and breast cancer | Bad | |||
| Normal stroma: (↑) Pancreatic stellate cells, smooth muscle actin, vimentin and desmin markers | Good | |||
| Activated stroma: (↑) Macrophages, tumour promotion and fibroblast activation-associated genes | Bad | |||
| Bailey et al. [10] | Mutational Transcriptional |
Primary PDAC tumour samples and rare acinar cell carcinoma (n = 382) PDAC exomes (n = 74) |
Squamous: Hypermethylation and (↓) pancreatic endodermal cell fate genes. TP53, KDM6A and TP63ΔN | Bad |
| Pancreatic progenitor: (↑) Pancreatic early development genes (PDX1) | Good | |||
| ADEX: (↑) K-RAS activation and pancreatic late development and differentiation genes | ||||
| Immunogenic: (↑) Immune suppression and strong immune infiltration | ||||
| Zhao et al. [34] | Transcriptional (metanalysis) | 1. Microarray datasets of PDAC primary tumour samples (n = 1268) TCGA (n = 172) GSE79670 (n = 51) TCGC PACA-AU (n = 71) MTAB-1791 (n = 195) ICGC array (n = 178) GSE71729 (n = 145) GSE62165 (n = 118) GSE62452 (n = 69) GSE57495 (n = 63) GSE60980 (n = 49) GSE77858 (n = 46) GSE55643 (n = 45) GSE15471 (n = 39) |
L1: (↑) Metabolic genes | |
| L2: (↑) Metabolic, cell proliferation and epithelium genes (CDKN2A) | Bad | |||
| L3: (↑) Collagen and ECM associated genes | ||||
| L4: (↑) Immune profile | Good | |||
| L5: (↑) Neuroendocrine and insulin related pathways | Good | |||
| L6: (↑) Metabolic and digestive enzyme genes | ||||
| Lomberk et al. [35] | Epigenetic | 1. PDXs (n = 24) 2. Clinical samples microarray datasets GSE71729 (n = 145) ICGC (n = 178) TCGA (n = 172) |
Classical: (↑) TFs involved in pancreatic development, metabolic regulators and Ras signalling | Good |
| Basal: (↑) TF proliferative and transcription nodes | Bad | |||
| Maurer et al. [36] | Transcriptional Computational modelling |
1. Primary PDAC tumour samples (n = 122) 2. Clinical samples microarray datasets GSE71729 (UNC) (n = 125) ICGC (n = 93) TCGA (n= 127) |
Classical: Classical Moffit | Good |
| Basal: Basal Moffit | Bad | |||
| Immune-rich: (↑) immune and interleukin levels | Good | |||
| ECM-rich: (↑) matrix extracellular pathways | Bad | |||
| Dijk et al. [37] | Transcriptional | 1. Primary PDAC tumour samples (n = 90) 2. Pancreatic cancer PDXs cohort (n = 14) 3. PDAC Cell lines cohort (n = 51) |
Epithelial: (↑) MYC, mitochondrial components and ribosome signature | Good |
| Mesenchymal: (↑) K-RAS, pathways related to EMT, stromal signalling and TGF-β | Bad | |||
| Compound pancreatic: Similar to the mesenchymal subtype and (↑) endocrine pathways | Good | |||
| Chan-Seng-Yue et al. [38] | Whole genome sequencing Transcriptional |
Laser capture microdissected samples from late-stage PDAC 1. WGS (n = 314) 2. Bulk RNAseq (n = 248) 3. Single-cell RNAseq (n = 15) |
Classical A/B: (↑) SMAD4 and GATA6 alterations | Good |
| Basal-like A/B: (↑) EMT and TGF-β pathways, loss of CDKN2A, TP53 mutations, K-RAS imbalance | Bad | |||
| Hybrid | Mid | |||
| Nicolle et al. [39] | Transcriptional | PDXs (n = 76) | Graded types between classical and basal based on tumour differentiation | Grade dependant |
For each classification, type of study, type and number of samples, dysregulated pathways and mutations and prognosis are described in each column. Up-regulated and down-regulated pathways are shown as (↑) and (↓), respectively. CAF, Cancer-Associated Fibroblast; EMT, Epithelial-to-Mesenchymal Transition; PDAC, Pancreatic Ductal Adenocarcinoma; PDX, Patient-Derived Xenograft; TF, Transcription Factor; WGS, Whole Genome Sequencing.