Profiling of GEPNETs

Table 4

Summary of expression profiling studies on ileal carcinoids.

Study	Tumor type (number)	Profiling platform	Main findings	Therapeutic implications
Duerr et al. [60] Endocr Relat Cancer	GI-NET (𝑛=6) (5 ileal carcinoids,1 colonic carcinoid; sporadic)	Expression array (Affymetrix U133)	GI-NETs have a different gene expression pattern from PNETs. Frequently upregulated genes in GI-NETs belong to “transporters” and “motor activity.” Validated genes in GI-NETs include ECM1, VMAT1 LGALS4, and RET	Candidates for targeted therapy include RET signaling
Arvidsson et al. [72] Endocr Relat Cancer	Ileal carcinoids (𝑛=5) (sporadic)	Expression array (Swegen, Lund University)	Ileal carcinoid express a large number of neuroendocrine markers including CHGA, SCGN, SYT13, DDC, SYN1, SCG, and VAMP2. Differentially expressed pathways include MAPK, Wnt, Hedghog, andNotch. Verified genes include APLP1 which correlates to tumor progression.	Candidates for targeted therapy include APLP1 Notch signalling
Leja et al. [73] Mod Pathol	Ileal carcinoids (𝑛=6) (sporadic)	Expression array (Affymetrix U133)	Overexpression of 94 genes and underexpression of 276 genes in ileal carcinoids (tumor versus normal ileal mucosa). Upregulated and verified genes include PNMA2, SPOCK1, SERPINA10, GRIA2, GPR112, OR51E1. Downregulation of CXCL14 and NKX2-3 during tumor progression.	Candidates for targeted therapy include GPR112 and OR51E1
Ruebel et al. [75] Mod Pathol	Ileal carcinoids (𝑛=16) (sporadic)	Expression array (QuantiMir)	Upregulation of miRNA-183, −488, and −19a + b and downregulation of miRNA −133a, −145, −146, −222, and −10b in ileal carcinoids (metastases versus primary). miRNA-133a is expressed in enterochromaffin cells and is downregulated in ileal carcinoids during tumor progression	—
Edfeldt et al. [74] Endocr Relat Cancer	Ileal carcinoids (𝑛=42) (sporadic)	Expression array (KTH Royal Institute of Technology)	Ileal carcinoids cluster in three groups by principal component analysis. Verified genes that were differentially expressed include TUSC2, RUNX1, TPH1, TGFBR2, and CDH6. Downregulation of ACTG2, GREM2, and REG3A during tumor progression.	—

For genes and proteins in bold, therapeutic agents are available for preclinical or clinical testing. GI-NET: gastrointestinal neuroendocrine tumor; PNET: pancreatic neuroendocrine tumor.