Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma

Table 1 The HGF signature genes

GeneSymbol	GeneName	Ratio^a	P value	Chromosome
From panel A: genes that are down-regulated only in sensitive tumors (n = 9)
GPLD1	Glycosylphosphatidylinositol specific phospholipase D1	0.48	0.0019391	14
NOVA2	Neuro-oncological ventral antigen 2	0.46	0.0026136	7
LRP5	Low density lipoprotein receptor-related protein 5	0.41	0.0028902	11
ARHGEF4	Rho guanine nucleotide exchange factor (GEF) 4	0.35	0.0013269	2
F11R	F11 receptor	0.33	0.0005396	1
ALDH5A1	Aldehyde dehydrogenase 5 family, member A1	0.31	0.0003027	6
SLIT3	Slit homolog 3 (Drosophila)	0.22	0.000271	11
TLR4	Toll-like receptor 4	0.088	2.59E−05	9
CTSZ	Cathepsin Z	0.081	0.0044628	20
From panel B: genes that are up-regulated only in sensitive tumors (n = 12)
HGF	Hepatocyte growth factor (hepapoietin A; scatter factor)	47.52	0.000534	7
AHR	Aryl hydrocarbon receptor	46.56	2.35E−05	7
MFAP4	Microfibrillar-associated protein 4	28.51	8.53E−05	17
DPT	Diptericin	9.37	0.0027492	2R
COL3A1	Collagen, type III, alpha 1	8.210	0.0012553	2
F2RL2	Coagulation factor II (thrombin) receptor-like 2	3.96	0.003144	5
LPXN	Leupaxin	3.86	0.0038993	11
DAB2	Dab, mitogen-responsive phosphoprotein, homolog 2	3.5	0.0035502	5
TBC1D8B	TBC1 domain family, member 8B (with GRAM domain)	2.7	0.0015932	X
GPHN	Gephyrin	2.63	0.0038916	6
C16orf45	Chromosome 16 open reading frame 45	1.99	0.0048897	16
CREB3L2	cAMP responsive element binding protein 3-like 2	1.87	0.0047229	7

By analyzing the mRNA expression datasets from TCGA GBM patients and those from preclinical xenograft models, 21 genes were found uniquely down- or up-regulated only in the sensitive tumors, providing a signature of an HGF network to identify tumors sensitive to MET inhibitors
^aRatio = average mRNA expression level in insensitive tumors/average mRNA expression level in sensitive tumors

ISSN: 1479-5876