Basic Study
Copyright ©The Author(s) 2017.
World J Gastroenterol. Feb 21, 2017; 23(7): 1189-1202
Published online Feb 21, 2017. doi: 10.3748/wjg.v23.i7.1189
Table 1 Primer of quantitative real-time polymerase chain reaction
IDPrimerSequence (5'to3')Base (bp)Tm (°C)GC
HIPK2ForwardCCCCGTGTACGAAGGTATGG2059.9060%
ReverseGGGATGTTCTTGCTCTGGCT2060.0355%
PDE3BForwardTGAGAGTTATGGCTGCCTGT2058.7250%
ReverseCTGAGGGGCATTTGTAGCCA2060.3055%
FGF2ForwardTCCACCTATAATTGGTCAAAGTGGT2559.9940%
ReverseCATCAGTTACCAGCTCCCCC2059.8260%
TWIST1ForwardATTCAAAGAAACAGGGCGTGG2159.3947.6%
ReverseCAGAGGTGTGAGGATGGTGC2060.3940%
ZEB2ForwardGCCTCTGTAGATGGTCCAGTGA2261.2154.6%
ReverseATCGCGTTCCTCCAGTTTTCT2160.0047.6%
VEGFCForwardCCCGCCTCTCCAAAAAGCTA2060.0455%
ReverseCGGGTGTCAGGTAAAAGCCT2059.9655%
SPHK1ForwardGCTGCGAAGTTGAGCGAAAA2060.0450%
ReverseCGTTCCCTACAGTGGCCTG1960.0863.2%
BAXForwardGCCCTTTTGCTTCAGGGTTT2059.2450%
ReverseCATCCTCTGCAGCTCCATGT2059.8255%
PTENForwardCAGGATACGCGCTCGGC1760.7370.6%
ReverseACAGCGGCTCAACTCTCAAA2057.8950%
HTRA1ForwardAGCCAAAGAGCTGAAGGACC2059.9655%
ReverseGACATCATTGGCGGAGACCA2060.1155%
CCL5ForwardTGCTGCTTTGCCTACATTGC2059.7650%
ReverseCTTGTTCAGCCGGGAGTCAT2060.0455%
TGM2ForwardCCTCTGTCTCTCCGGGAACC2061.3265%
ReverseTGGCAACCAGGGGTCCTAT1960.2357.9%
TLR4ForwardCTCGGTCAGACGGTGATAGC2059.9760%
ReverseTTTAGGGCCAAGTCTCCACG2059.6855%
ACTBForwardCTCACCATGGATGATGATATCGC2359.1347.8%
ReverseAGGAATCCTTCTGACCCATGC2159.7952.4%
Table 2 Different expressed mRNAs enriched by KOBAS
TermDatabaseP valueInput gene symbols
Gastric cancerKEGG DISEASE0.0016DCC, CD44, CDH1, VEGFC, EGF, TGFA
Skin diseasesKEGG DISEASE0.0078DSP, TGM1, CCL5, IL31RA, SPINK5, HLA, FERMT1, KRT14, CTSC, COL17A1, LAMA3, REEP1, RIN2, ALOXE3, ABCC6, WNT10A, FBLN5
Skin and soft tissue diseasesKEGG DISEASE0.0078DSP, TGM1, CCL5, IL31RA, SPINK5, HLA, FERMT1, KRT14, CTSC, COL17A1, LAMA3, REEP1, RIN2, ALOXE3, ABCC6, WNT10A, FBLN5
Macular degenerationKEGG DISEASE0.0140C3, FBLN5, CFH, TLR4
Cancers of the digestive systemKEGG DISEASE0.0439DCC, CD44, CDH1, VEGFC, EGF, TGFA
Familial thoracic aortic aneurysm and dissection (TAAD)KEGG DISEASE0.0459MYLK, TGFBR1
HypomagnesemiaKEGG DISEASE0.0459TRPM6, EGF
Multiple epiphyseal dysplasia (MED)KEGG DISEASE0.0459COL9A3, MATN3
Transient neonatal diabetes mellitus (TNDM)KEGG DISEASE0.0459PLAGL1, ZFP57
Non-syndromic autosomal dominant mental retardationKEGG DISEASE0.0461EPB41L1, DOCK8, PACS1, SMARCA4
Cardiac hypertrophyNHGRI GWAS Catalog0.0028PLXNA2, GRIK2, COL17A1, JAG1, SNAP25, BTBD3, SLX4IP
Response to fenofibrate (adiponectin levels)NHGRI GWAS Catalog0.0046OAS2, PMEPA1, SHANK2, SCUBE1, SLC30A4, PCK1
Complement C3 and C4 levelsNHGRI GWAS Catalog0.0094HLA, CFHR3, CFH, C3
Neutrophil countNHGRI GWAS Catalog0.0119PLCB4, TGFA, FGGY, PDGFD, PSD3
Nephropathy(idiopathic membranous)NHGRI GWAS Catalog0.0137HLA, ITGB6, PLA2R1
Sleep durationNHGRI GWAS Catalog0.0195PLLP, TMC5, ADAMTS14
Airflow obstructionNHGRI GWAS Catalog0.0259HYKK, LEF1, SERPINB8, GPR126, MAP3K13, PTPRD
Cystic fibrosis severityNHGRI GWAS Catalog0.0265HLA, EHF, AHRR
Metabolite levels (5-HIAA/ MHPG Ratio)NHGRI GWAS Catalog0.0265PIEZO2, ROBO2, ADAM12
Bronchopulmonary dysplasiaNHGRI GWAS Catalog0.0296PLXDC2, ZNF770, SPOCK1, TRPS1, RASGRF1, HIVEP3
Major depressive disorderNHGRI GWAS Catalog0.0346PCLO, SLC6A15, ENOX1, SYPL2, IGFBP1, IGFBP3, C12orf5, ATXN1, PIEZO2, TRPS1, RASGEF1B, FGF12, KCNH5
IgA nephropathyNHGRI GWAS Catalog0.0346HLA, ACOXL, TNFSF13
Pulmonary function declineNHGRI GWAS Catalog0.0368MUSK, CSMD1, RORA, FLRT2
Palmitic acid (16:0) plasma levelsNHGRI GWAS Catalog0.0368SCD, CNN3, GRIK2, PTPRD
Male-pattern baldnessNHGRI GWAS Catalog0.0439AUTS2, EDA2R, AR
Response to citalopram treatmentNHGRI GWAS Catalog0.0439LAMA1, RORA, EGFLAM
HyperlipidemiaFunDO0.0050IRS1, CCL5, C3, PAPPA, TXNIP, APOC1, F3, SCD
ThrombocytopeniaFunDO0.0068GATA1, CCL5, ITGB3, IL11, CXCL8, MPL
FibromyalgiaFunDO0.0126MAOB, CXCL8, BDNF, IGFBP3
CirrhosisFunDO0.0209RBP4, KRT18, IGFBP3, KRT8, EGF, F3, FGF2IGFBP1
Hepatitis CFunDO0.0321CD274, CCL5, RBP4, MKI67, CXCL8, KRT18, TLR4, KRT8, FGF2
ThalassemiaFunDO0.0345LCN2, CXCL8, ANK2, KIR3DL1, MUC1
Gingival overgrowthFunDO0.0417EDN1, IL15, FGF7
Pulmonary fibrosisFunDO0.0474CSF1, BDNF, MMP7, EDN1, CCL5, ERBB3
Ovary cancerFunDO0.0477LCN2, IL15, CXCL8, FGF7, CASP1
Esophageal tumorFunDO0.0477CD274, TSPAN8, FRAT1, PDCD1LG2, FGF7
HyperlipidemiaGAD0.0093CCL5, HLA, CXCL8, CD22, TNFRSF1B, CD19
ThrombocytopeniaGAD0.0114CSMD1, DOCK4, GALNTL6, SOBP, PLXDC2, SESN3, ADAMTS5, EHF, TMC5, LPL, CD109, FAM117B, PDE1C, TAGLN, PTN, FGD4, DYNC2H1, GNG4, MUSK, FBLN5, CCDC54, TTC9, PMEPA1, TLR4, ANK3, EDA2R, APOC1, BMP2, TOX3, NRG1, ITPK1, PTPRD, KLF6, PAM, PTPRU, LEPR, IKZF2, LHX5, MCTP2, ANKRD50, SEMA6D, PLXNA2, DPYD, GRIK2, SRGAP3, ACOXL, TDRKH, FAM135B, VEGFC, CHST2
FibromyalgiaGAD0.0136GLI3, CELF2, VWA3B, PLXDC2, EDNRA, EDN1, JUN, DOCK8, DCLK2, BTBD3, DCN, CD74, EGFLAM, TLL1, TLR4, BMP2, PTPRD, ANK2, PTPRU, JADE2, IGF2BP2, PAPPA, DOCK2, KLK4, FAM49A, RGS3, AATK, FN1, IGSF10, NCOA7, SCIN, TNS1, FAM135B, MUC16, ADAM19, ATXN1, MTUS2, NXNL2, KCNQ3, ANPEP, CDH2
CirrhosisGAD0.0204IRS1, CCL5, ITGB3, NPR1, NPR3, APOC1, LPL
Hepatitis CGAD0.0258DPYD, CELF4, CELF2, FAM117B, TDRKH, LPCAT4, FBLN5, SOBP, PMEPA1, CSMD1, STOX1, CACNB2, CADM1, VEGFC, SLC7A11, LPL, CD109, MCTP2, SLC24A2, PTPRD, ITPK1
ThalassemiaGAD0.0362MCTP2, PSD3, CCDC54, ROBO2, ELOVL6
Gingival overgrowthGAD0.0419PLXNA2, ATXN1, IGF2BP2, ABCA13, FN1
Pulmonary fibrosisGAD0.0420CREG2, GALNTL6, LINC01550, KIF16B, SH3BGR, TRPS1, PDE1C, NCKAP5, TNFRSF21, RYR3, MAGEC2, EDIL3, CXCL16, MCF2, DTD1, GPC5, KLF6, IKZF2, KCNH5, AJAP1, BTBD3, PHACTR2, ITPK1, IGSF10, SRGAP3, C12orf75, ABI3BP, FOS, SCUBE1
Ovary cancerGAD0.0426CELF4, TRPS1, TWIST1, PQLC2L, MAL2, PSD3, RCAN2, SUPT3H, TGFA, TMEM131L, HIVEP3, CSMD1, ROBO2, CCDC54, PRNP, APOC1, HRK, GPC5, AR, FN1, ABCA13, F2RL2, KLF6, IGF2BP2, LEPREL1, GNG4, SNAP25, MCTP2, FAM49A, ANKRD50, CACNA2D1, PLXNA2, ELOVL6, RUNX2, SCN8A, ATXN1, ID2, SLC24A2, CMTM7, LINGO2
Esophageal tumorGAD0.048CACNA2D1, SLC46A3, CHST2, PKDCC, PPID, CDH2
Table 3 Cisplatin resistance pathway and input gene (P < 0.05, FC ≥ 2.0)
PathwayInput geneFold changeRegulationGenomic coordinatesCyto band
PI3K-Akt signaling pathwayLAMA12.60826UpChr18:6958512-6956742hs|18p11.31
LAMA12.75269UpChr18:6942035-6941976hs|18p11.31
GNG42.09356UpChr1:235714443-235714384hs|1q42.3
ITGB32.96629UpChr17:45389027-45389086hs|17q21.32
ITGB67.72783UpChr2:160964233-160958330hs|2q24.2
VEGFC2.92538UpChr4:177604882-177604823hs|4q34.3
PDGFD2.42861UpChr11:103778445-103778386hs|11q22.3
IRS12.00967UpChr2:227596677-227596618hs|2q36.3
GNGT12.04779UpChr7:93536149-93540155hs|7q21.3
CSF12.25620UpChr1:110466137-110466196hs|1p13.3
EGF4.76437UpChr4:110932689-110932748hs|4q25
FGF23.02437UpChr4:123819331-123819390hs|4q28.1
FGF22.99240UpChr4:123819317-123819376hs|4q28.1
FN12.31254UpChr2:216288895-216288217hs|2q35
COL4A62.08497UpChrx:107399109-107399050hs|Xq22.3
FGF1210.99211UpChr3:191860574-191860515hs|3q28
GNG112.01984UpChr7:93555764-93555823hs|7q21.3
FGF72.19252UpChr15:49776810-49776869hs|15q21.2
LAMA32.56116DownChr18:21534735-21534794hs|18q11.2
IFNA212.30808DownChr9:21166331-21166272hs|9p21.3
CREB3L32.40183DownChr19:4172219-4172278hs|19p13.3
TLR42.13271DownChr9:120476856-120476915hs|9q33.1
COL6A22.89458DownChr21:47546086-47546145hs|21q22.3
CD192.09302DownChr16:28950600-28950659hs|16p11.2
LPAR53.83177DownChr12:6728794-6728735hs|12p13.31
COL4A42.11177DownChr2:227867523-227867464hs|2q36.3
PCK14.49558DownChr20:56141030-56141089hs|20q13.31
VTN3.82587DownChr17:26694806-26694747hs|17q11.2
GNGT216.48365DownChr17:47284034-47283975hs|17q21.32
IL2RG2.87954DownChrx:70328539-70328480hs|Xq13.1
COL5A37.53410DownChr19:10070602-10070543hs|19p13.2
FGF1317.08866DownChrx:137713947-137713888hs|Xq26.3
MAPK signaling pathwayFLNC4.57879DownChr7:128498538-128498597hs|7q32.1
FLNC4.81302DownChr7:128498476-128498535hs|7q32.1
CACNB27.83293DownChr10:18787305-18787364hs|10p12.31
RASGRF14.87152DownChr15:79254554-79254495hs|15q25.1
FOS2.17501DownChr14:75748214-75748273hs|14q24.3
JUN2.04000DownChr1:59246570-59246511hs|1p32.1
RASGRP23.10358DownChr11:64508971-64508912hs|11q13.1
FGF1317.08866DownChrx:137713947-137713888hs|Xq26.3
TGFBR12.93035UpChr9:101916322-101916381hs|9q22.33
TGFBR14.76437UpChr4:110932689-110932748hs|4q25
EGF4.76437UpChr4:110932689-110932748hs|4q25
FGF1210.99211UpChr3:191860574-191860515hs|3q28
MAP3K132.25019UpChr3:185161379-185165590hs|3q27.2
FGF23.02437UpChr4:123819331-123819390hs|4q28.1
FGF22.99240UpChr4:123819317-123819376hs|4q28.1
MAP2K72.08267UpChr19:7979302-7979361hs|19p13.2
FGF72.19252UpChr15:49776810-49776869hs|15q21.2
CACNG48.83585UpChr17:65028139-65028198hs|17q24.2
CACNG42.94145UpChr17:65029115-65029174hs|17q24.2
CACNB42.14311UpChr2:152694239-152694180hs|2q23.3
GADD45A2.56659UpChr1:68153371-68153430hs|1p31.3
BDNF2.32411UpChr11:27679959-27679900hs|11p14.1
BDNF2.30323UpChr11:27677072-27677013hs|11p14.1
CACNA2D12.09452UpChr7:81579504-81579445hs|7q21.11
Notch signaling pathwayMAML22.03379UpChr11:95712434-95712375hs|11q21
JAG13.20086UpChr20:10619120-10619061hs|20p12.2
MAML32.57919UpChr4:140810806-140810747hs|4q31.1
DTX49.99859DownChr11:58975615-58975674hs|11q12.1
ErbB signaling pathwayEGF4.76437UpChr4:110932689-110932748hs|4q25
NRG12.77996UpChr8:32474390-32585512hs|8p12
MAP2K72.08267UpChr19:7979302-7979361hs|19p13.2
JUN2.04000DownChr1:59246570-59246511hs|1p32.1
ERBB35.29571DownChr12:56482380-56482439hs|12q13.2
ERBB38.12050DownChr12:56496160-56496219hs|12q13.2
TGFA2.37427DownChr2:70675378-70675319hs|2p13.3
Jak-STAT signaling pathwayIL114.21849UpChr19:55875847-55875788hs|19q13.42
IL152.92970UpChr4:142654431-142654490hs|4q31.21
SOCS22.00180UpChr12:93969799-93969858hs|12q22
SPRY15.95682UpChr4:124324494-124324553hs|4q28.1
LEPR2.90187UpChr1:66102129-66102188hs|1p31.3
IL2RG2.87954DownChrx:70328539-70328480hs|Xq13.1
MPL3.41581DownChr1:43819826-43819885hs|1p34.2
NF-kappaB signaling pathwayCXCL22.03846UpChr4:74963044-74962985hs|4q13.3
CXCL89.97781UpChr4:74609265-74609324hs|4q13.3
TLR42.13271DownChr9:120476856-120476915hs|9q33.1
HIF-1 signaling pathwayEDN12.39081UpChr6:12296672-12296731hs|6p24.1
EDN12.46437UpChr6:12296218-12296277hs|6p24.1
EGF4.76437UpChr4:110932689-110932748hs|4q25
TLR42.13271DownChr9:120476856-120476915hs|9q33.1
MicroRNAs in cancerIRS12.00967UpChr2:227596677-227596618hs|2q36.3
ZEB23.32563UpChr2:145146320-145146261hs|2q22.3
ZEB22.70558UpChr2:145182422-145182363hs|2q22.3
CD442.02409UpChr11:35253812-35253871hs|11p13
RECK2.25018UpChr9:36124319-36124378hs|9p13.3
ITGB32.96629UpChr17:45389027-45389086hs|17q21.32
SERPINB52.61864UpChr18:61172218-61172277hs|18q21.33
GLS2.36144UpChr2:191829716-191829775hs|2q32.2
GLS2.07371UpChr2:191827822-191827881hs|2q32.2
ERBB35.29571DownChr12:56482380-56482439hs|12q13.2
ERBB38.12050DownChr12:56496160-56496219hs|12q13.2
Table 4 Dysregulated mRNAs (P < 0.05, FC ≥ 2.0) associated with cisplatin resistance
Gene symbolP valueFC (abs)RegulationGenenameRef.
FGF70.000352.19252UpFibroblast growth factor 7PMID: 22990650
HIPK22.63E-064.06213UpHomeodomain interacting protein kinase 2PMID: 24846322
EDN19.94E-052.46437UpEndothelin 1PMID: 21220476
CBS0.001082.29340UpCystathionine-beta-synthasePMID: 24236104
PDE3B0.0002910.44998UpPhosphodiesterase 3B, cgmp-inhibitedPMID: 24133626
E2F50.000412.42888UpE2F transcription factor 5, p130-bindingPMID: 22193543
PIN10.001042.13293UpPeptidylprolyl cis/trans isomerase, NIMA-interacting 1PMID: 26820938
EGF0.003464.76437UpEpidermal growth factorPMID: 27086487
CSF10.000252.25620UpColony stimulating factor 1 (macrophage)PMID: 22005523
PCNA0.001032.17028UpProliferating cell nuclear antigenPMID: 24474685
HIPK22.63E-064.06213UpHomeodomain interacting protein kinase 2PMID: 24846322
ENTPD60.000112.43726UpEctonucleoside triphosphate diphosphohydrolase 6 (putative)PMID: 21519793
AKR1C10.000972.29646UpAldo-keto reductase family 1, member C1PMID: 23165153, PMID: 17266043
ASNS0.001722.19491UpAsparagine synthetase (glutamine-hydrolyzing)PMID: 23956056, PMID: 17409444
BDNF0.000622.32411UpBrain-derived neurotrophic factorPMID: 22276165, PMID: 17044982
CABYR0.010892.55664UpCalcium binding tyrosine-(Y)-phosphorylation regulatedPMID: 24362251
FGF22.15E-062.99240UpFibroblast growth factor 2 (basic)PMID: 12894531
SLC7A111.95E-052.93256UpSolute carrier family 7 member 11PMID: 24516043
TUBB30.000462.00213UpTubulin, beta 3 class IIIPMID: 25107571
TWIST10.001802.96340UpTwist family bhlh transcription factor 1PMID: 22673193, PMID: 22245869
JAG19.41E-053.20086UpJagged 1PMID: 24659709
ANXA110.000312.36619DownAnnexin A11PMID: 19484149, PMID: 17982121
CCL52.67E-055.05630DownChemokine (C-C motif) ligand 5PMID: 26983899
FGF130.0004417.08866DownFibroblast growth factor 13PMID: 24113164
IGFBP37.48E-052.92508DownInsulin-like growth factor binding protein 3PMID: 20023704
KLK60.000662.24596DownKallikrein-related peptidase 6PMID: 23307575
SLC7A84.50E-055.36735DownSolute carrier family 7 member 8PMID: 23462296
TGM22.88E-056.24520DownTransglutaminase 2PMID: 21424127, PMID: 24828664
TLR40.001142.13271DownToll-like receptor 4PMID: 21616060, PMID: 22583829
XAF10.024053.20613DownXIAP associated factor 1PMID: 25824780, PMID: 25240826
TCEA20.000613.65969DownTranscription elongation factor A (SII), 2PMID: 16142353