Pancreatic neuroendocrine tumors: A case-based evidence review

Table 2 Biomarkers for the diagnosis of pNEN[23]

Circulating biomarkers
Non-specific biomarkers	Specific to functional pNEN	Specific to nonfunctional pNEN
Chromogranin A	Insulin	Pancreatic polypeptide
Pancreastatin	Glucagon	Human chorionic gonadotropin
Chromogranin B	Gastrin	Neurotensin
Neuron-specific enolase	Somatostatin	Ghrelin
Alpha fetoprotein	Vasoactive intestinal peptide	Calcitonin
	Growth hormone or GHRH
	Adrenocorticotropic hormone
Immunohistochemical biomarkers
Differentiation markers	Site of origin markers	Prognostic markers
Chromogranin A	NESP55	ATRX/DAXX
Synaptophysin	PGR	SSTR2a
INSM1	PDX1	PD-L1
	ARX
	ISL1
Molecular biomarkers
Circulating tumor cells (CTCs)
Circulating cell-free DNA (cfDNA)
Circulating microRNAs (miRNAs)
Circulating transcripts (NETest score)
G protein-coupled receptor-associated sorting protein 1 (GPRASP1)
Delta-like protein 3 (DLL3)
Tumor-associated macrophages (TAMs)
Glucose transporter 1 (GLUT1)

INSM1: Insulinoma-associated protein 1; NESP55: Neuroendocrine secretory protein 55; PGR: Progesterone receptor; PDX1: Pancreatic and duodenal homeobox 1; ISL-2: Insulin gene enhancer binding protein 2; ATRX/DAXX: Alpha-thalassemia/mental retardation X-linked and death domain-associated protein; SSTR2a: Somatostatin receptors 2a; PD-L1: Programmed cell death ligand 1.