http://jcps.bjmu.edu.cn

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (8): 511-524.DOI: 10.5246/jcps.2014.08.067

• 【研究论文】 • 上一篇    下一篇

Differential signaling regulatory networks governing hormone refractory prostate cancers

Sujit Nair1,2, Celine Liew2,3, Tin Oo Khor2, Li Cai4, Ah-Ng Kong2*   

  1. 1. Amrita Cancer Discovery Biology Laboratory and Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham University, Ponekkara P.O., Kochi-682041, Kerala, India
    2. Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
    3. Department of Pharmacy, National University of Singapore, Singapore-117543, Republic of Singapore
    4. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
  • 收稿日期:2014-04-08 修回日期:2014-04-14 出版日期:2014-08-31 发布日期:2014-04-23
  • 通讯作者: Tel.: 848-445-6369/8, Fax: 732-445-3134
  • 基金资助:
    National Institutes of Health (Grant No. RO1 CA118947 and RO1 CA152826 to Ah-Ng Tony Kong and R21 CA133675 to Li Cai).

Differential signaling regulatory networks governing hormone refractory prostate cancers 

Sujit Nair1,2, Celine Liew2,3, Tin Oo Khor2, Li Cai4, Ah-Ng Kong2*   

  1. 1. Amrita Cancer Discovery Biology Laboratory and Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham University, Ponekkara P.O., Kochi-682041, Kerala, India
    2. Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
    3. Department of Pharmacy, National University of Singapore, Singapore-117543, Republic of Singapore
    4. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
  • Received:2014-04-08 Revised:2014-04-14 Online:2014-08-31 Published:2014-04-23
  • Contact: Tel.: 848-445-6369/8, Fax: 732-445-3134
  • Supported by:
    National Institutes of Health (Grant No. RO1 CA118947 and RO1 CA152826 to Ah-Ng Tony Kong and R21 CA133675 to Li Cai).

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摘要：

To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer (HRPC), we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rv1 and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer (PCa) cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site (TFBS) signatures to dissect HRPC regulatory networks. We generated graphical representationsof global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ‘target hubs’ were identified in the current study including AP-1, NF-қB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia (HG-PIN) and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ‘target hubs’ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.

关键词: Prostate cancer, Signaling network, Target hub, Regulatory network, Biomarker, Transcription Factor Binding Site

Abstract:

To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer (HRPC), we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rv1 and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer (PCa) cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site (TFBS) signatures to dissect HRPC regulatory networks. We generated graphical representationsof global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ‘target hubs’ were identified in the current study including AP-1, NF-қB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia (HG-PIN) and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ‘target hubs’ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.

Key words: Prostate cancer, Signaling network, Target hub, Regulatory network, Biomarker, Transcription Factor Binding Site

中图分类号: 

Supporting:

 

Accession
Gene Symbol
Gene
22Rv1
Fold
DU 145
Fold
LNCaP
Fold
MDA PCa 2b
Fold
PC-3
Fold
NM_016816
OAS1
2',5'-oligoadenylate synthetase 1, 40/46kDa
-25.54
-9.04
-36.07
-22.53
-15.79
NM_016817
OAS2
2'-5'-oligoadenylate synthetase 2, 69/71kDa
-101.85
-104.88
-71.59
-50.03
-78.66
NM_006187
OAS3
2'-5'-oligoadenylate synthetase 3, 100kDa
-13.91
-3.67
-19.38
-25.69
-15.74
NM_003733
OASL
2'-5'-oligoadenylate synthetase-like
-32.59
-4.25
-20.61
-43.51
-14.35
NM_148914
ABHD11
abhydrolase domain containing 11
27.14
4.06
15.43
17.64
10.59
NM_017977
AIM1L
absent in melanoma 1-like
-14.01
-13.87
-13.58
-5.52
-11.55
NM_005622
ACSM3
acyl-CoA synthetase medium-chain family member 3
25.78
2.75
21.68
16.21
3.49
BE897866
ACADSB
acyl-Coenzyme A dehydrogenase, short/branched chain
21.95
7.64
51.14
55.38
15.86
BG435404
ARL4C
ADP-ribosylation factor-like 4C
-47.22
-5.16
-29.81
-14.13
-7.97
U05598
AKR1C2
aldo-keto reductase family 1, member C2
-3.36
-8.06
-81.48
-113.30
-29.33
AL137586
ANAPC7
anaphase promoting complex subunit 7
6.47
8.21
12.21
8.46
11.03
AW173504
AR
androgen receptor (dihydrotestosterone receptor)
24.69
-1.92
47.95
52.57
-1.03
NM_001630
ANXA8
annexin A8
-51.06
-24.51
-53.40
-28.74
-36.75
NM_004041
ARRB1
arrestin, beta 1
16.08
1.04
31.22
39.14
9.79
AF120274
ARTN
artemin
-5.20
-17.43
-7.13
-47.47
-32.12
AI928342
ASRGL1
asparaginase like 1
103.44
68.07
24.99
338.55
70.89
NM_017935
BANK1
B-cell scaffold protein with ankyrin repeats 1
20.06
7.77
59.44
34.82
9.93
NM_004335
BST2
bone marrow stromal cell antigen 2
-25.23
-61.23
-49.59
-126.36
-112.44
NM_000055
BCHE
butyrylcholinesterase
2.46
121.32
50.06
-1.39
118.99
NM_001257
CDH13
cadherin 13, H-cadherin (heart)
-50.69
-36.80
-96.19
-21.71
-40.70
AA743820
CAPN14
calpain 14
-20.92
-10.74
-12.27
-15.30
-13.54
AF038567
CTAG1A
cancer/testis antigen 1A
209.64
1.00
6.43
36.71
1.00
BC042510
CEL
carboxyl ester lipase (bile salt-stimulated lipase)
-30.28
-19.22
-3.60
-12.56
-11.17
AI719655
CASP1
caspase 1, apoptosis-related cysteine peptidase
-4.44
-8.35
-6.86
-8.16
-6.57
AI246687
CTSC
cathepsin C
-38.36
-10.05
-91.33
-127.99
-6.91
NM_001766
CD1D
CD1d molecule
-23.46
-16.53
-56.53
-8.94
-56.53
AV700298
CD44
CD44 molecule (Indian blood group)
-8.94
-8.27
-17.19
-12.56
-8.72
AL519710
CADM1
cell adhesion molecule 1
23.55
119.41
32.80
1.57
285.99
NM_024053
CENPM
centromere protein M
14.73
8.21
7.82
5.55
7.23
AF030514
CXCL11
chemokine (C-X-C motif) ligand 11
-77.51
-51.51
-38.88
-22.26
-73.49
NM_006536
CLCA2
chloride channel, calcium activated, family member 2
-26.05
-27.03
-23.89
-14.89
-25.52
AF195624
CHPT1
choline phosphotransferase 1
35.81
8.06
18.62
17.94
9.17
NM_000745
CHRNA5
cholinergic receptor, nicotinic, alpha 5
7.78
12.35
7.63
6.24
14.04
AF059274
CSPG5
chondroitin sulfate proteoglycan 5 (neuroglycan C)
21.64
19.08
36.61
22.46
11.80
BE568660
CHURC1
churchill domain containing 1
5.61
13.71
7.25
7.30
7.46
AW264204
CLDN11
claudin 11 (oligodendrocyte transmembrane protein)
63.69
70.63
-3.04
-2.77
49.88
BE791251
CLDN3
claudin 3
95.11
44.40
105.92
437.99
48.90
M25915
CLU
clusterin
31.42
7.54
1.10
21.72
12.25
AI889941
COL4A6
collagen, type IV, alpha 6
-22.67
-40.14
-48.15
-9.20
-20.12
NM_000094
COL7A1
collagen, type VII, alpha 1
-14.07
-11.68
-18.00
-16.61
-18.62
X04697
CFH
complement factor H
-39.94
-22.07
-39.94
-39.94
-26.28
NM_015198
COBL
cordon-bleu homolog (mouse)
8.77
18.76
12.68
17.21
14.60
AF007162
CRYAB
crystallin, alpha B
-10.16
-13.13
-10.84
-21.51
-11.84
NM_000496
CRYBB2
crystallin, beta B2
1.00
1.00
1.00
156.83
1.00
BF448201
CUL5
cullin 5
17.90
57.78
70.63
47.53
51.87
NM_001759
CCND2
cyclin D2
-104.35
-61.43
-191.96
-97.63
-54.61
AA922068
CDK6
cyclin-dependent kinase 6
-5.63
-5.39
-14.33
-16.13
-8.13
AW444761
CDKN2B
cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
-18.23
-6.28
-77.00
-96.89
-5.45
NM_001262
CDKN2C
cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)
10.52
9.09
5.59
3.16
11.70
NM_005213
CSTA
cystatin A (stefin A)
-144.29
-426.21
-165.89
-148.84
-397.66
NM_000784
CYP27A1
cytochrome P450, family 27, subfamily A, polypeptide 1
10.17
12.74
11.00
8.08
12.66
NM_018665
DDX43
DEAD (Asp-Glu-Ala-Asp) box polypeptide 43
1.44
131.78
37.27
1.45
91.72
NM_014314
DDX58
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
-54.53
-4.76
-47.44
-22.23
-18.52
AF196571
DLL1
delta-like 1 (Drosophila)
-13.73
-61.59
-3.53
-20.18
-32.94
NM_001941
DSC3
desmocollin 3
-22.46
-15.44
-16.85
-29.42
-19.29
AF064771
DGKA
diacylglycerol kinase, alpha 80kDa
-5.24
-6.90
-26.75
-5.24
-7.68
AU148057
DKK3
dickkopf homolog 3 (Xenopus laevis)
-106.37
-6.60
-165.41
-219.87
-13.04
AI144299
DHFR
dihydrofolate reductase
18.90
8.33
12.04
7.91
6.05
AI620209
DPP7
Dipeptidyl-peptidase 7
14.45
2.66
17.31
12.98
5.21
X93921
DUSP7
dual specificity phosphatase 7
-8.23
-30.38
-8.56
-7.32
-31.28
AC005393
DYRK1B
dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B
7.96
14.60
11.71
11.09
12.20
AL096710
DST
dystonin
-68.73
-177.40
-171.32
-120.16
-71.88
AA609053
ENPP5
ectonucleotide pyrophosphatase/phosphodiesterase 5
12.71
20.71
29.35
16.67
7.29
M74921
EDNRB
endothelin receptor type B
13.44
14.11
11.76
9.14
14.95
BC000686
EPDR1
ependymin related protein 1 (zebrafish)
17.01
33.67
1.56
12.04
43.54
NM_005228
EGFR
epidermal growth factor receptor
-23.87
-6.65
-21.54
-7.05
-12.06
NM_001423
EMP1
epithelial membrane protein 1
-16.42
-7.47
-29.44
-17.67
-29.30
AA633203
EPSTI1
epithelial stromal interaction 1 (breast)
-13.53
-17.01
-22.07
-13.54
-15.37
AL120674
ESCO2
establishment of cohesion 1 homolog 2 (S. cerevisiae)
20.15
7.25
11.18
2.22
9.56
NM_005103
FEZ1
fasciculation and elongation protein zeta 1 (zygin I)
-20.54
-10.19
-77.20
-76.99
-13.38
AL832251
FBXO18
F-box protein, helicase, 18
-0.05
25.44
15.12
20.55
32.69
AU152635
FECH:
ferrochelatase (protoporphyria)
21.74
5.25
29.63
22.17
6.81
AB016517
FGF5
fibroblast growth factor 5
-34.83
-34.83
-34.83
-34.83
-34.83
NM_013281
FLRT3
fibronectin leucine rich transmembrane protein 3
-5.20
-10.07
-43.97
-34.42
-17.31
NM_004476
FOLH1
folate hydrolase (prostate-specific membrane antigen) 1
138.34
1.32
390.46
448.93
1.83
BF438173
FST
follistatin
-60.98
-163.08
-208.34
-57.88
-189.16
NM_004496
FOXA1
forkhead box A1
12.87
3.81
13.06
15.50
3.89
AI676059
FOXQ1
forkhead box Q1
-15.54
-9.98
-11.41
-5.74
-20.95
NM_006018
GPR109B
G protein-coupled receptor 109B
-23.95
-99.38
-56.79
-99.38
-12.94
W67511
GPR115
G protein-coupled receptor 115
-32.62
-32.84
-42.53
-8.19
-45.57
BC000181
GPR160
G protein-coupled receptor 160
14.04
12.48
22.35
37.86
13.62
NM_023915
GPR87
G protein-coupled receptor 87
-60.52
-24.61
-145.06
-60.95
-90.17
AW183080
GPR92
G protein-coupled receptor 92
-35.76
-21.12
-34.92
-14.65
-35.55
NM_004961
GABRE
gamma-aminobutyric acid (GABA) A receptor, epsilon
-6.41
-9.31
-10.71
-23.63
-9.19
N46350
GDAP1
ganglioside-induced differentiation-associated protein 1
10.19
3.72
7.18
16.00
6.83
M86849
GJB2
gap junction protein, beta 2, 26kDa
-133.01
-145.24
-249.89
-177.13
-110.03
AI694073
GJB6
gap junction protein, beta 6
-485.64
-264.73
-213.17
-291.00
-572.90
BC002557
GATA2
GATA binding protein 2
20.94
4.45
28.96
49.23
5.35
BE675337
GSN
gelsolin (amyloidosis, Finnish type)
-104.87
-68.10
-68.10
-104.87
-81.93
NM_012413
QPCT
glutaminyl-peptide cyclotransferase (glutaminyl cyclase)
-7.27
-3.30
-192.43
-40.25
-11.82
AL527430
GSTM3
glutathione S-transferase M3 (brain)
9.86
7.10
19.40
21.41
7.05
NM_000852
GSTP1
glutathione S-transferase pi
-66.56
-6.24
-73.26
-69.50
-6.17
NM_000853
GSTT1
glutathione S-transferase theta 1
6.43
12.27
5.69
10.23
9.72
BF432254
GLYATL1
glycine-N-acyltransferase-like 1
97.60
1.70
65.04
78.44
-1.48
NM_002510
GPNMB
glycoprotein (transmembrane) nmb
-8.52
-20.83
-6.76
-4.07
-11.92
X61094
GM2A
GM2 ganglioside activator
-13.12
-11.48
-4.33
-4.97
-10.16
NM_016548
GOLM1
golgi membrane protein 1
1.95
23.30
10.38
14.35
14.34
AL137763
GRHL3
grainyhead-like 3 (Drosophila)
-36.55
-14.23
-9.34
-16.44
-13.75
AF261715
PSMAL
growth-inhibiting protein 26
60.46
1.23
193.75
229.75
2.49
BM666010
GNG4
guanine nucleotide binding protein (G protein), gamma 4
47.30
38.18
1.65
1.11
32.68
AW014593
GBP1
guanylate binding protein 1, interferon-inducible, 67kDa
-60.08
-8.70
-36.06
-55.12
-40.02
AL136680
GBP3
guanylate binding protein 3
-58.72
-18.78
-60.61
-13.02
-57.85
AW392952
GBP4
guanylate binding protein 4
-22.16
-14.39
-11.54
-4.35
-22.16
AK023754
HES2
hairy and enhancer of split 2 (Drosophila)
-14.92
-16.40
-16.54
-16.27
-17.51
NM_016323
HERC5
hect domain and RLD 5
-22.73
-4.25
-15.57
-17.41
-6.18
NM_003483
HMGA2
high mobility group AT-hook 2
-12.05
-23.50
-49.50
-27.00
-12.63
NM_014707
HDAC9
histone deacetylase 9
-19.74
-17.43
-40.60
-25.50
-17.93
AI246769
HOXA9
homeobox A9
-8.92
-14.06
-68.17
-54.63
-17.78
BF062550
HOXB13
homeobox B13
48.31
-4.61
55.12
64.52
-3.23
NM_017409
HOXC10
homeobox C10
28.51
33.51
2.54
1.12
38.16
NM_004503
HOXC6
homeobox C6
13.54
10.04
25.48
12.86
9.18
AW299531
HOXD10
homeobox D10
-31.02
-35.35
-58.49
-24.46
-25.37
BC001387
HRASLS3
HRAS-like suppressor 3
62.70
78.17
47.51
238.97
44.60
NM_016245
HSD17B11
hydroxysteroid (17-beta) dehydrogenase 11
15.08
11.33
1.76
16.14
10.69
NM_001553
IGFBP7
insulin-like growth factor binding protein 7
-242.44
-347.59
-250.06
-341.20
-523.01
AV733308
ITGA6
integrin, alpha 6
-62.11
-6.88
-23.30
-5.50
-8.26
NM_000213
ITGB4
integrin, beta 4
-45.44
-4.77
-24.84
-13.75
-16.02
NM_000888
ITGB6
integrin, beta 6
-29.49
-30.01
-26.69
-5.19
-37.46
BF513121
ITGB8
integrin, beta 8
-7.22
-27.15
-107.12
-25.65
-52.75
AA749101
IFITM1
interferon induced transmembrane protein 1 (9-27)
-83.96
-55.65
-104.15
-125.96
-121.95
NM_006435
IFITM2
interferon induced transmembrane protein 2 (1-8D)
-17.47
-3.69
-8.49
-11.15
-52.59
NM_022168
IFIH1
interferon induced with helicase C domain 1
-26.99
-10.09
-15.42
-7.74
-30.42
NM_004030
IRF7
interferon regulatory factor
-19.81
-4.17
-6.50
-10.24
-12.11
AU144284
IRF6
interferon regulatory factor 6
-25.52
-34.57
-8.23
-3.83
-53.14
NM_005532
IFI27
interferon, alpha-inducible protein 27
-244.57
-34.89
-214.29
-168.40
-224.19
NM_022873
IFI6
interferon, alpha-inducible protein 6
-250.97
-8.75
-24.39
-53.71
-19.60
AF208043
IFI16
interferon, gamma-inducible protein 16
-109.01
-18.51
-84.87
-201.47
-257.39
NM_001548
IFIT1
interferon-induced protein with tetratricopeptide repeats 1
-779.95
-4.30
-61.25
-2119.70
-14.87
BE888744
IFIT2
interferon-induced protein with tetratricopeptide repeats 2
-14.32
-7.66
-17.86
-18.19
-10.94
NM_001549
IFIT3
interferon-induced protein with tetratricopeptide repeats 3
-22.60
-4.99
-17.57
-19.36
-17.58
N47725
IFIT5
interferon-induced protein with tetratricopeptide repeats 5
-9.90
-4.60
-7.17
-9.07
-5.30
NM_012420
IFIT5
interferon-induced protein with tetratricopeptide repeats 5
-8.53
-4.99
-6.39
-7.03
-7.26
NM_006084
ISGF3G
interferon-stimulated transcription factor 3, gamma 48kDa
-22.39
-7.37
-29.25
-26.90
-12.74
BE563442
IL1RN
interleukin 1 receptor antagonist
-28.91
-22.30
-5.98
-4.67
-21.63
M15329
IL1A
interleukin 1, alpha
-121.86
-91.83
-163.18
-173.36
-105.82
NM_000576
IL1B
interleukin 1, beta
-45.61
-23.18
-51.53
-30.37
-23.73
AL578102
IL20RB
interleukin 20 receptor beta
-64.83
-5.52
-74.74
-29.44
-45.70
NM_005547
IVL
involucrin
-7.88
-8.38
-8.63
-8.67
-8.62
NM_006633
IQGAP2
IQ motif containing GTPase activating protein 2
2.98
17.97
13.89
42.01
16.92
AI928035
IRX2
iroquois homeobox 2
-108.53
-121.68
-9.34
-218.53
-77.04
BC002710
KLK10
kallikrein-related peptidase 10
-74.89
-61.21
-92.99
-350.24
-194.51
AF243527
KLK5
kallikrein-related peptidase 5
-17.38
-22.13
-14.10
-16.53
-14.72
AU155415
KLK7
kallikrein-related peptidase 7
-15.39
-7.53
-12.18
-10.65
-8.73
NM_007196
KLK8
kallikrein-related peptidase 8
-457.43
-66.10
-223.14
-457.43
-59.95
BC002690
KRT14
keratin 14
-452.88
-1664.70
-173.10
-47.19
-357.82
NM_002275
KRT15
keratin 15
-115.43
-98.12
-772.21
-18.31
-33.79
NM_000422
KRT17
keratin 17
-76.07
-57.10
-57.94
-96.62
-71.05
NM_000424
KRT5
keratin 5
-165.28
-863.87
-568.05
-136.84
-225.51
AL569511
KRT6A
keratin 6A
-426.03
-503.08
-347.95
-522.30
-273.23
L42612
KRT6B
keratin 6B
-38.75
-80.78
-46.41
-36.54
-43.11
AI668605
KLB
klotho beta
18.75
41.35
9.08
19.44
8.96
BC012919
KLF7
Kruppel-like factor 7 (ubiquitous)
-6.06
-23.76
-65.01
-6.34
-24.11
NM_000227
LAMA3
laminin, alpha 3
-125.88
-5.33
-13.28
-17.77
-15.37
L25541
LAMB3
laminin, beta 3
-134.23
-3.31
-105.47
-79.92
-5.64
NM_005562
LAMC2
laminin, gamma 2
-209.40
-9.45
-340.91
-34.52
-26.86
NM_024679
LPHN1
latrophilin 1
14.24
17.43
23.29
10.15
12.33
U50748
LEPR
leptin receptor
-16.88
-6.39
-38.45
-20.56
-9.51
AK027231
LIMCH1
LIM and calponin homology domains 1
5.75
10.11
28.95
31.13
5.58
AV709727
LONRF2
LON peptidase N-terminal domain and ring finger 2
34.18
9.03
23.84
54.39
31.56
NM_014400
LYPD3
LY6/PLAUR domain containing 3
-293.91
-4.71
-134.69
-15.76
-10.26
NM_014398
LAMP3
lysosomal-associated membrane protein 3
-36.11
-12.04
-39.33
-19.83
-12.03
AU149305
MMP14
matrix metallopeptidase 14 (membrane-inserted)
-18.97
-8.04
-17.16
-16.30
-7.09
NM_024302
MMP28
matrix metallopeptidase 28
-16.71
-15.41
-13.37
-35.25
-33.64
BC003408
MAGEA12
melanoma antigen family A, 12
239.35
-1.00
255.91
201.46
1.48
NM_005361
MAGEA2
melanoma antigen family A, 2
172.01
4.48
216.63
114.79
1.77
BC000340
MAGEA3
melanoma antigen family A, 3
95.16
-1.54
89.87
74.61
1.02
U10691
MAGEA6
melanoma antigen family A, 6
284.97
1.03
269.67
228.42
1.03
AF216650
MTAP
methylthioadenosine phosphorylase
20.36
14.79
9.99
7.02
11.07
NM_014033
METTL7A
methyltransferase like 7A
127.17
-2.33
46.97
42.28
-2.19
AI674759
MAPKBP1
mitogen activated protein kinase binding protein 1
-9.69
-4.25
-5.59
-12.33
-7.00
BE967311
MCC
mutated in colorectal cancers
-68.62
-6.26
-84.26
-48.81
-18.27
AI318120
MAZ
MYC-associated zinc finger protein
14.30
13.93
17.49
4.64
7.58
NM_005368
MB
myoglobin
42.58
7.21
46.01
111.61
4.49
NM_002462
MX1
myxovirus (influenza virus) resistance 1
-157.24
-15.89
-91.15
-92.74
-44.16
AF119848
NDUFA2
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2
9.33
24.24
19.00
21.33
29.11
NM_015678
NBEA
neurobeachin
14.01
6.88
6.20
22.11
10.19
BC001606
NCF2
neutrophil cytosolic factor 2 (65kDa)
-31.05
-27.92
-38.94
-32.75
-72.04
AF247704
NKX3-1
NK3 homeobox 1
68.90
5.72
54.01
76.77
2.98
NM_017617
NOTCH1
Notch homolog 1, translocation-associated
-6.47
-9.60
-7.29
-8.91
-16.07
NM_021963
NAP1L2
nucleosome assembly protein 1-like 2
72.01
13.29
144.02
32.94
1.92
AI381524
NAP1L4
Nucleosome assembly protein 1-like 4
-12.40
-12.40
-12.40
-12.40
-12.40
AL833418
PNLIPRP3
pancreatic lipase-related protein 3
-69.04
-202.43
-93.69
-88.87
-51.00
NM_002820
PTHLH
parathyroid hormone-like hormone
-20.09
-123.00
-37.74
-38.34
-24.05
BC003096
PDLIM4
PDZ and LIM domain 4
-14.57
-64.24
-21.71
-8.35
-14.19
L10343
PI3
peptidase inhibitor 3, skin-derived (SKALP)
-19.12
-12.57
-15.05
-13.85
-26.81
NM_002705
PPL
periplakin
-78.62
-6.40
-15.27
-20.76
-7.89
AB028127
PIGM
phosphatidylinositol glycan anchor biosynthesis, class M
14.93
5.85
11.67
6.02
5.74
AA888858
PDE3B
Phosphodiesterase 3B, cGMP-inhibited
13.04
10.45
9.57
18.26
17.82
NM_021105
PLSCR1
phospholipid scramblase 1
-9.84
-3.60
-224.26
-192.22
-5.78
AI378979
PKP1
plakophilin 1 (ectodermal dysplasia/skin fragility syndrome)
-139.13
-720.45
-187.75
-3.34
-209.79
NM_006207
PDGFRL
platelet-derived growth factor receptor-like
24.60
58.50
19.60
11.00
30.42
AI718937
KCTD12
potassium channel tetramerisation domain containing 12
-6.60
-5.50
-76.09
-57.88
-42.43
U73191
KCNJ15
potassium inwardly-rectifying channel, subfamily J, member 15
-74.08
-61.76
-19.57
-219.41
-108.16
D82346
KCNQ2
potassium voltage-gated channel, KQT-like subfamily, member 2
28.58
14.10
23.91
1.68
18.34
NM_006115
PRAME
preferentially expressed antigen in melanoma
5.37
13.27
26.11
26.68
7.32
NM_002675
PML
promyelocytic leukemia
-122.23
-3.27
-23.15
-23.69
-7.42
NM_002736
PRKAR2B
protein kinase, cAMP-dependent, regulatory, type II, beta
-0.01
58.54
89.56
188.69
62.68
AI888150
PPP1R9A
protein phosphatase 1, regulatory (inhibitor) subunit 9A
40.96
21.80
10.64
15.44
36.41
AB032983
PPM1H
protein phosphatase 1H (PP2C domain containing)
15.87
16.92
13.58
28.54
10.09
AI631833
PTPRJ
protein tyrosine phosphatase, receptor type, J
9.82
21.04
6.51
42.31
11.53
NM_022337
RAB38
RAB38, member RAS oncogene family
-144.22
-7.37
-98.64
-156.05
-4.82
AI805050
RAB6B
RAB6B, member RAS oncogene family
4.85
23.40
49.25
44.82
19.80
BC005153
RPH3AL
rabphilin 3A-like (without C2 domains)
-1.06
19.01
12.49
26.11
12.23
AW189843
RSAD2
radical S-adenosyl methionine domain containing 2
-18.15
-16.13
-27.89
-37.68
-19.57
AL096776
RHOU
ras homolog gene family, member U
40.44
5.77
12.94
37.51
7.66
AK000776
ROR1
receptor tyrosine kinase-like orphan receptor 1
-1.46
25.59
4.89
22.77
37.97
AI824113
RGS12
regulator of G-protein signaling 12
-6.04
-4.98
-5.80
-7.87
-4.97
NM_014882
ARHGAP25
Rho GTPase activating protein 25
-31.17
-31.17
-31.17
-31.17
-31.17
AJ131212
RNASE7
ribonuclease, RNase A family, 7
-89.11
-55.35
-89.11
-31.16
-28.20
NM_024539
RNF128
ring finger protein 128
-10.84
-6.26
-11.49
-263.10
-199.65
BF056204
RNF157
ring finger protein 157
145.67
233.27
136.43
24.37
185.86
AI677701
RBM24
RNA binding motif protein 24
1.19
41.83
17.61
19.35
44.01
AF312386
RUNX1
runt-related transcription factor 1
15.24
9.51
18.46
12.51
12.40
NM_005978
S100A2
S100 calcium binding protein A2
-448.88
-27.01
-332.20
-361.20
-67.90
NM_002961
S100A4
S100 calcium binding protein A4
-202.92
-3.03
-110.20
-56.99
-9.78
NM_002964
S100A8
S100 calcium binding protein A8
-2670.91
-128.39
-4059.78
-2218.46
-4059.78
NM_002965
S100A9
S100 calcium binding protein A9
-153.41
-10.57
-310.86
-157.64
-147.79
AI745526
SPDEF
SAM pointed domain containing ets transcription factor
46.66
1.65
21.12
69.42
1.49
AW470178
SCEL
sciellin
-17.11
-5.01
-29.53
-17.66
-6.91
AI332407
SFRP1
secreted frizzled-related protein 1
-55.23
-4.18
-22.67
-56.73
-4.28
NM_003118
SPARC
secreted protein, acidic, cysteine-rich (osteonectin)
-64.77
-53.23
-34.49
-130.50
-251.64
NM_005410
SEPP1
selenoprotein P, plasma, 1
48.22
7.67
41.51
91.28
2.41
M23699
SAA1
serum amyloid A1
-507.23
-14.10
-182.46
-507.23
-207.88
NM_005627
SGK
serum/glucocorticoid regulated kinase
-29.73
-5.74
-15.43
-38.10
-7.92
AF022654
SHOX2
short stature homeobox 2
38.16
12.44
22.92
6.55
47.29
BC002704
STAT1
signal transducer and activator of transcription 1, 91kDa
-92.22
-7.22
-31.34
-58.45
-9.32
BF680588
STEAP2
six transmembrane epithelial antigen of the prostate 2
20.56
2.05
31.70
16.44
1.95
AV730849
SLAIN1
SLAIN motif family, member 1
171.53
60.87
102.88
83.72
16.02
NM_033438
SLAMF9
SLAM family member 9
-18.31
-23.25
-8.71
-23.25
-23.25
NM_005585
SMAD6
SMAD family member 6
101.25
173.03
66.79
105.02
90.49
NM_005987
SPRR1A
small proline-rich protein 1A
-21.94
-43.04
-18.62
-16.36
-27.34
NM_006945
SPRR2B
small proline-rich protein 2B
-9.43
-14.01
-16.71
-9.45
-13.00
BF575466
SPRR3
small proline-rich protein 3
-35.84
-29.38
-83.03
-36.35
-29.19
AI572079
SNAI2
snail homolog 2 (Drosophila)
-17.97
-19.19
-39.40
-12.80
-13.99
NM_004696
SLC16A4
solute carrier family 16, member 4 (monocarboxylic acid transporter 5)
-4.06
-91.47
-45.66
-86.64
-63.26
NM_020041
SLC2A9
solute carrier family 2 (facilitated glucose transporter), member 9
-7.56
-7.07
-7.63
-6.76
-5.96
AI279062
SLC22A15
solute carrier family 22 (organic cation transporter), member 15
-13.17
-19.32
-25.29
-4.02
-29.00
NM_030631
SLC25A21
solute carrier family 25 (mitochondrial oxodicarboxylate carrier), member 21
8.54
251.44
8.58
10.53
278.27
NM_022154
SLC39A8
solute carrier family 39 (zinc transporter), member 8
13.49
8.05
5.38
10.35
8.36
NM_003759
SLC4A4
solute carrier family 4, sodium bicarbonate cotransporter, member 4
2.07
14.95
50.38
41.23
13.41
AA631143
SLC45A3
solute carrier family 45, member 3
35.60
3.83
44.33
66.87
3.35
AA876372
SLC7A2
solute carrier family 7 (cationic amino acid transporter, y+ system), member 2
42.26
-0.85
15.81
17.63
8.35
NM_013272
SLCO3A1
solute carrier organic anion transporter family, member 3A1
-12.58
-10.40
-15.81
-17.49
-16.04
NM_003113
SP100
SP100 nuclear antigen
-131.33
-5.50
-11.73
-6.46
-6.78
NM_014474
SMPDL3B
sphingomyelin phosphodiesterase, acid-like 3B
12.55
19.65
28.88
25.93
23.89
AI989530
SGEF
Src homology 3 domain-containing guanine nucleotide exchange factor
4.82
9.27
29.50
19.94
11.90
AI808807
SOX7
SRY (sex determining region Y)-box 7
-19.95
-18.16
-34.09
-15.30
-15.52
AW328672
STARD10
StAR-related lipid transfer (START) domain containing 10
6.52
5.98
29.60
19.58
16.61
AA741307
SAMD9
sterile alpha motif domain containing 9
-124.65
-3.99
-33.85
-54.31
-228.87
AI122754
STS
steroid sulfatase (microsomal), isozyme S
9.10
8.87
18.81
18.27
5.37
BE379761
STON2
Stonin 2
-5.02
-9.42
-10.12
-5.87
-9.47
AL034418
SULF2
sulfatase 2
-20.42
-22.35
-21.10
-17.11
-34.88
AW663885
SUHW2
suppressor of hairy wing homolog 2 (Drosophila)
10.31
6.56
10.69
12.17
14.44
BC000731
SYNGR1
synaptogyrin 1
10.57
17.08
15.73
1.77
15.37
NM_016524
SYT17
synaptotagmin XVII
6.36
26.90
-1.54
46.47
21.01
AA158731
TNS4
tensin 4
-45.50
-45.50
-45.50
-45.50
-45.50
NM_000361
THBD
thrombomodulin
-11.89
-7.06
-18.07
-17.25
-8.15
AF021834
TFPI
tissue factor pathway inhibitor
8.19
38.71
75.58
-1.09
62.78
NM_003265
TLR3
toll-like receptor 3
-9.67
-6.60
-7.49
-5.56
-7.22
AK025084
TOX3
TOX high mobility group box family member 3
219.85
1.25
40.74
327.87
1.29
AL008730
TRAF3IP2
TRAF3 interacting protein 2
-7.69
-5.44
-6.06
-5.10
-5.83
BC001830
TGFB1I1
transforming growth factor beta 1 induced transcript 1
-8.29
-4.51
-66.24
-36.92
-14.12
AA806283
TMEM154
transmembrane protein 154
-65.76
-89.80
-29.22
-11.83
-521.75
AI087937
TMEM40
transmembrane protein 40
-43.62
-21.71
-41.21
-43.96
-57.99
AA054642
TMEM56
transmembrane protein 56
11.09
18.38
8.44
22.19
26.17
AF162690
TTR
transthyretin (prealbumin, amyloidosis type I)
33.70
15.44
40.67
16.77
20.82
AA083478
TRIM22
tripartite motif-containing 22
-68.85
-590.91
-112.16
-40.68
-90.86
NM_012101
TRIM29
tripartite motif-containing 29
-51.63
-35.11
-59.67
-25.81
-78.05
NM_003810
TNFSF10
tumor necrosis factor (ligand) superfamily, member 10
-26.42
-19.14
-50.00
-10.41
-30.82
AF026071
PLEKHG5
pleckstrin homology domain containing, family G, member 5
-11.30
-3.88
-5.82
-11.30
-11.30
AF091627
TP63
tumor protein p63
-38.64
-34.77
-22.67
-32.41
-18.75
BE551138
ARTS-1
type 1 tumor necrosis factor receptor shedding aminopeptidase regulator
-40.93
-14.14
-9.23
-37.02
-41.02
AK022859
UNC5B
unc-5 homolog B (C. elegans)
-28.89
-78.91
-31.41
-6.10
-70.72
AI754423
VGLL3
vestigial like 3 (Drosophila)
-44.90
-38.45
-47.05
-28.81
-63.04
BC036233
WDR66
WD repeat domain 66
-14.28
-10.90
-7.31
-12.46
-6.03
BC005056
WBSCR18
Williams Beuren syndrome chromosome region 18
8.51
4.54
11.28
10.62
5.94
NM_030761
WNT4
wingless-type MMTV integration site family, member 4
-6.16
-5.46
-7.36
-10.03
-6.58
AA167449
XIST
X (inactive)-specific transcript
-15.57
-31.30
-16.58
-4.60
-24.55
AF193855
ZIC2
Zic family member 2 (odd-paired homolog, Drosophila)
163.82
9.16
255.13
218.58
73.08
NM_007150
ZNF185
zinc finger protein 185 (LIM domain)
-18.96
-4.20
-29.85
-15.03
-7.98
NM_024702
ZNF750
zinc finger protein 750
-158.61
-112.12
-96.79
-101.47
-112.12
AK097019
ZNF781
zinc finger protein 781
7.81
19.72
12.62
20.80
20.79

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