Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update

Table 5 Summary of single gene expression studied reported in gallbladder cancer

Studied single genes	Expression pattern	Studied population	Ref.
TP53	Expression (20%-70%)	India, Slovenia, Greece, Taiwan, Japan, Chile	[75,84-86,102-106]
p16	Overexpression	South Korea	[107]
FHIT	Expression loss (45%-75%)	Japan, Chile	[108,109]
ERBB2	Overexpression (25%-64%)	India, Japan, China, South Korea	[66,103,110,111]
	Expressed in 9.4%cases of well differentiated and stage II to stage IV tumors	India	[90]
RB	20% cases allelic loss	Japan	[54,112]
	4%-14%- loss of expression
CDKN1A	Reduced expression 49% cases	Japan	[113]
Cyclin D1, Cyclin E	Overexpression (41%-49%)	Japan	[114,115]
COX2	Over-expressed	Slovenia, Japan, Chile	[104,116,117]
BCL2	Over-expressed	Japan	[118]
CKIT	Expression 45%	Japan	[119]
SOX-4	Overexpression	China	[120]
Chemokine (C-X-C motif) ligand 12	Increased expression	South Korea	[121]
CXCR4, CXCR7	Increased expression	China	[122]
hedgehog pathway components (Shh, Ptch1 and Gli1)	Shh: 81.7% of cases expressed	China	[123]
	Ptch1: 75.3% of cases
	Gli1: 70.0% of cases
CD56, CD99	Altered expression	South Korea	[124]
CD97, CD55	CD97: 69.6% of cases expressed	China	[125]
	CD55: 65.2% of cases
HMGA2 and CD9	HMGA2 positive expression	China	[126]
	CD9 negative expression
cholecystokinin type-A	44.1% of cases expressed	India	[127]
vascular endothelial growth factor-A	53.6% of cases expressed	China	[128]
VEGF-C, VEGF-D	VEGF-C: 64.0% of cases	China	[129]
	VEGF-D: 62.0% of cases
Tumor endothelial marker 8 protein	Increased expression	India	[130]
L1 cell adhesion molecule	Increased expression	South Korea	[131]
Tissue factor pathway inhibitor-2	Down-regulated	China	[132]
HIF-1α	Increased expression	China	[133]
VHL	Reduces expression
ERCC1(excision repair cross-complementing 1)	High expression in best differentiated tumors	Chile	[134]
NF-E2-related factor 2 (Nrf2)	Increased expression	China	[135]
CD34 , CA15-3	Highly expressed in stroma and in epithelium	Italy	[136]
ADAM-17	Overexpression	China	[137]
Cdx2	Aberrant expression	Japan	[138]
TLR4	Expressed in glandular and luminal epithelium	China	[139]
MiRNA	Loss of Dicer and Drosha expression	China	[140]
Inducible Nitric Oxide Synthase iNOS	Expressed	China	[141]
Prostate stem cell antigen (PSCA)	Down-regulated	Japan, China	[142]
OCT-4	Down-regulated	China	[143]
hTERT/Telomerase	Expressed in 56.66% cases	India	[144]
Aquaporins (AQPs)	Positive expression	Japan	[145]
Ornithine decarboxylase (ODC) and glutamate decarboxylase 65 (GAD65)	Overexpression	China	[146]
Alpha-methylacyl coenzyme A (racemase) AMACR	Overexpression	Taiwan	[147]
Sonic Hh (Shh)	Elevated expression	Japan	[148]
TGF-β induced miR-182	Overexpression	China	[149]
SLP-2	Overexpression	China	[150]
TMPRSS4	Higher expression	China	[151]
zinc finger X-chromosomal protein	Suppressed	China	[152]
multidrug resistance-associated protein 2 (MRP2)	Overexpression	South Korea	[153]
HuR	Overexpression	Taiwan	[154]
miR-155	Overexpression	Japan	[155]
LAPTM4B-35	Overexpressed(76%)	China	[156]
p27, P21	p21 (75% cases) and p27 (25% cases)	Jordan	[157]
Thymidylate synthase (TS)	Low expression	Japan	[158]
CD146	Elevated expression	China	[159]
AEG-1	Highly expressed (63.4%)	China	[160]
CCKAR	Expression increased (76.6%)	India	[127]
Nemo-like kinase (NLK)	Overexpression of NLK	China	[161]
C-erbB2	Overexpression (9.4%)	India	[90]
Phospho-mTOR expression	Positive expression (64.1%)	Chile	[162]
human telomerase reverse transcriptase (hTERT)	Expression increased	India	[163]
Phosphoglycerate kinase 1 (PGK1)	Decreased expression (54.7%)	China	[164]
Notch 1 and Notch 3	Positive expression	China	[165]
CCK-A	Decreased expression	India	[166]
3-phosphoinositide-dependent protein kinase 1 (PDK1)	Positively expressed	China	[167]
Zinc finger X-chromosomal protein (ZFX)	Overexpression	China	[151]
miR-138	Over expression	China	[168]
HSP gp96	Expression (90.7%)	China	[169]
Long non-coding RNA-LET	Overexpression	China	[170]
Survivin	higher expression (2.9- fold)	India	[171]
Long non-coding RNA CCAT1	Overexpressed	China	[172]
TEM8	Expression increased	India	[130]
Fhit,MIh1, P53	Reduced expression of Fhit and Mlh1 protein and Overexpression of P53	Japan	[108]
NDRG2, CD24	NDRG2 down-regulation, CD24 up-regulation	China	[173]
IL-6	Overexpressed	China	[174]
SLP-2	Overexpression	China	[150]
BCL6, p19(ARF)	BCL6 overexpression , p19 (ARF) Low Expression	Taiwan	[175]
VEGF-A	High expression of VEGF-A	Chile	[176]
MALAT1	Upregulation of MALAT1	China	[177]
miR-182	Upregulation of miR-182	China	[149]
miR-155	High expression level of miR-155	Japan	[155]
p53, S100A4, p27, p16, RB, Smad4, FHIT, E-cadherin and PML	p53 and S100A4 overexpressed,	South Korea	[178]
	Loss of p27, p16, RB, Smad4, FHIT, E-cadherin and PML expression
PEG10, TSG101	PEG10 and TSG101 overexpressed	China	[179]
CK7, CK20	CK7 (69.05%), CK20 (28.57%) expressed	Greece	[180]