Overexpression of 66 transcripts (≥3-fold versus normal islets) Underexpression of 119 transcripts(≤3-fold versus normal islets) Verified proteines include IGFBP3, Fibronectin, p21, and CD99
Candidate pathways for targeted therapy include IGF signaling
PNET (all well-differentiated, F-PNET, and NF-PNET–5 benign, 7 malignant)
Expression array (Affymetrix U133)
Overexpression of 65 genes (≥3-fold malignant versus benign) Underexpression of 57 genes (≤3-fold malignant versus benign) Verified proteins include MET and IGFBP3, which are overexpressed in metastatic tumors
Candidates for targeted therapy include IGF signaling and MET tyrosine kinase
Overexpression of 45 genes (PNET versus normal pancreas), underexpression of 148 genes (PNET versus normal pancreas) Apoptosis-related genes frequently downregulated. Verified genes include FGF9, IER3, PHLDA2, IAPP, SST
Overexpression of 667 genes and underexpression of 323 genes (PNETs versus pancreatic islets) Verified genes include BIN1, SERPINA10, LCK, BST2 Highly similar expression profile of primaries and metastases.
Candidates for targeted therapy include LCK (Src family of PTKs) and BST2
Distinct pattern of miRNA distinguish PNETs from normal pancreas. 87 miRNA upregulated and 8 miRNA downregulated in PNET versus normal pancreas Expression of miR-103 and miR-107, and lack of miR-155 distinguish PNET from normal pancreas. miR-204 is primarily expressed in insulinoma. miR-21 is associated with high proliferation and liver metastases.
Overexpression of 311 genes in PNET (PNET versus normal pancreas) including neuroendocrine markers, CHGA, CHGB, SYP, PAM, DDC, and SSTR1. High Expression of AXL, MAFB and AXIN2
Candidates for targeted therapy include AXIN2 and Wnt signaling
Overexpression of 110 genes and underexpression of 120 genes (malignant versus benign tumors). Validated genes include PRSS2,CTRB1, SERPINA1, AGT, and CFB. SERPINA1 (alpha-1-antitryspin) is a marker of malignancy in insulinoma
PNET forms “benign” and “malignant”clusters differing in “transcription regulation” and “binding”. Validated genes upregulated in malignant cluster include FEV, ADCY2, NR4A2, and GADD45β. Expression pattern of PNET is different from GI-NETs. PDGFR- β is frequently activated (phosphorylated) in PNET.
Unsupervised hierarchical clustering separates NF-PNET from insulinoma. TSC2 and PTEN are downregulated in PNET and associated with short survival. SSTR2 is upregulated in NF-PNET. FGF13 expression in PNET correlates with metastatic potential.
Candidates for targeted therapy include AKT-mTOR pathway and SSTR2
For genes and proteins in bold, therapeutic agents are available for preclinical or clinical testing. F-PNET: functioning PNET; GI-NET: gastrointestinal neuroendocrine tumor; MEN1: multiple endocrine neoplasia type 1; NF-PNET: non-functioning PNET; PDEC: poorly differentiated endocrine carcinoma; PNET: pancreatic neuroendocrine tumor; WDET: well-differentiated endocrine tumor; WDEC: well differentiated endocrine carcinoma.