Table 1.

Recently identified makers regarding pancreatic cancer stroma

Stroma associated Markers	Functional description	Expression pattern vs. normal tissue	Prognostic implications	reference
syndecan-1	Transmembrane receptor; cell-cell and cell-matrix interactions	upregulated	Lack of stromal expression predicted a better prognosis	[128]
SPARC	Extracellular matrix glycoprotein; cell-matrix interactions and collagen binding	upregulated	overexpression is associated with poor outcome	[129] [130]
Periostin	A ligand for α-V/β-3 and α-V/β-5 integrin; support adhesion and migration of epithelial cells	upregulated	N/A	[131]
Activated stroma index (ASI)	Ratio of α-smooth muscle actin-stained area to collagen-stained area	upregulated	Upregulation was associated with a worse prognosis	[132]
TGFβ1	A cytokine within stroma; initiate and perpetuate desmoplastic reaction	upregulated	a negative prognostic factor	[130]
Type IV collagen	A collagen derived from stroma; forms a supramolecular network in the basement membrane that influences cell adhesion, migration and differentiation of epithelial cells	upregulated	Persisting high levels in circulation after surgery indicates a quick relapse and poor survival	[133]
thrombospondin-1	an adhesive glycoprotein in stroma; mediate cell-cell and cell-matrix interactions	upregulated	Strong expression indicates poor prognosis	[134]
PINCH	A cysteine-histidine-rich integrin-associated protein; facilitate the survival, malignant transformation and invasion of tumor cells	upregulated	Higher expression correlates with poor survival	[135]
CD4+CD25+ regulatory T cells	Inflammatory cells; a central role in self-tolerance and suppress effective antitumor immune responses	upregulated	Low prevalence correlates with better prognosis	[136]
syndecan-2	A single transmembrane domain protein; coreceptor allows for interaction with a large variety of ligands	upregulated	Stromal syndecan-2 has no influence on survival	[137]
CD10	A cell membrane-associated metalloproteinase; a marker for stromal stem cells	upregulated	Stromal CD10 expression is associated with poor prognosis	[138]
GATA-3+/T-bet+ tumor-infiltrating lymphoid	Inflammatory cells; regulate immune response within pancreatic cancer stroma	upregulated	An independent predictive marker correlates with poor survival	[139]
CD40/CD40L co-signaling molecules	Protein on antigen presenting cells and its corresponding ligand; reverse immune suppression and drive antitumor T cell response	downregulated	N/A	[140]
Rac1	A small signaling G protein; required for early metaplastic changes and eoplasia-associated actin rearrangements	upregulated	Deletion significantly prolonged survival in mouse models	[141]
Cxcr2	a member of the G-protein-coupled receptor family; combines with cxc in stromal fibroblasts to enhance the malignancy of pancreatic cancer	upregulated	Inhibition leads to improved survival in mouse models	[142]
Dendritic cells related markers	A list of markers specifically expressed in dendritic cells	downregulated	Low level expression indicates short survival	[143]
palladin	a component of actin-containing microfilaments; control cell shape, adhesion and contraction	upregulated	N/A	[144]
human macrophage metalloelastase	A member of human matrix metalloproteinase family; critical for the degradation of extracellular matrix proteins	upregulated	Worsen the prognosis of pancreatic cancer	[145]
PDGFRβ	a cell surface tyrosine kinase receptor; initiate and perpetuate desmoplastic reaction	upregulated	higher expression matched shorter prognosis	[146]
osteopontin	an extracellular structural protein; a potential marker for tumor-infiltrating macrophages and detectable in serum	Upregulated	N/A	[147]
EGFR	cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands; affect stroma formation	upregulated	Correlates with poor prognosis and disease progression	[108]
VEGF	a signal protein; stimulate vasculogenesis and angiogenesis	upregulated	Predictor for both liver metastasis and poor prognosis;	[148]

N/A: not available.