Dysregulation of mRNA profile in cisplatin-resistant gastric cancer cell line SGC7901

doi:10.3748/wjg.v23.i7.1189

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Basic Study

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

ID	Primer	Sequence (5'to3')	Base (bp)	Tm (°C)	GC
HIPK2	Forward	CCCCGTGTACGAAGGTATGG	20	59.90	60%
	Reverse	GGGATGTTCTTGCTCTGGCT	20	60.03	55%
PDE3B	Forward	TGAGAGTTATGGCTGCCTGT	20	58.72	50%
	Reverse	CTGAGGGGCATTTGTAGCCA	20	60.30	55%
FGF2	Forward	TCCACCTATAATTGGTCAAAGTGGT	25	59.99	40%
	Reverse	CATCAGTTACCAGCTCCCCC	20	59.82	60%
TWIST1	Forward	ATTCAAAGAAACAGGGCGTGG	21	59.39	47.6%
	Reverse	CAGAGGTGTGAGGATGGTGC	20	60.39	40%
ZEB2	Forward	GCCTCTGTAGATGGTCCAGTGA	22	61.21	54.6%
	Reverse	ATCGCGTTCCTCCAGTTTTCT	21	60.00	47.6%
VEGFC	Forward	CCCGCCTCTCCAAAAAGCTA	20	60.04	55%
	Reverse	CGGGTGTCAGGTAAAAGCCT	20	59.96	55%
SPHK1	Forward	GCTGCGAAGTTGAGCGAAAA	20	60.04	50%
	Reverse	CGTTCCCTACAGTGGCCTG	19	60.08	63.2%
BAX	Forward	GCCCTTTTGCTTCAGGGTTT	20	59.24	50%
	Reverse	CATCCTCTGCAGCTCCATGT	20	59.82	55%
PTEN	Forward	CAGGATACGCGCTCGGC	17	60.73	70.6%
	Reverse	ACAGCGGCTCAACTCTCAAA	20	57.89	50%
HTRA1	Forward	AGCCAAAGAGCTGAAGGACC	20	59.96	55%
	Reverse	GACATCATTGGCGGAGACCA	20	60.11	55%
CCL5	Forward	TGCTGCTTTGCCTACATTGC	20	59.76	50%
	Reverse	CTTGTTCAGCCGGGAGTCAT	20	60.04	55%
TGM2	Forward	CCTCTGTCTCTCCGGGAACC	20	61.32	65%
	Reverse	TGGCAACCAGGGGTCCTAT	19	60.23	57.9%
TLR4	Forward	CTCGGTCAGACGGTGATAGC	20	59.97	60%
	Reverse	TTTAGGGCCAAGTCTCCACG	20	59.68	55%
ACTB	Forward	CTCACCATGGATGATGATATCGC	23	59.13	47.8%
	Reverse	AGGAATCCTTCTGACCCATGC	21	59.79	52.4%

GC: Gastric cancer.

Table 2 Different expressed mRNAs enriched by KOBAS

Term	Database	P value	Input gene symbols
Gastric cancer	KEGG DISEASE	0.0016	DCC, CD44, CDH1, VEGFC, EGF, TGFA
Skin diseases	KEGG DISEASE	0.0078	DSP, TGM1, CCL5, IL31RA, SPINK5, HLA, FERMT1, KRT14, CTSC, COL17A1, LAMA3, REEP1, RIN2, ALOXE3, ABCC6, WNT10A, FBLN5
Skin and soft tissue diseases	KEGG DISEASE	0.0078	DSP, TGM1, CCL5, IL31RA, SPINK5, HLA, FERMT1, KRT14, CTSC, COL17A1, LAMA3, REEP1, RIN2, ALOXE3, ABCC6, WNT10A, FBLN5
Macular degeneration	KEGG DISEASE	0.0140	C3, FBLN5, CFH, TLR4
Cancers of the digestive system	KEGG DISEASE	0.0439	DCC, CD44, CDH1, VEGFC, EGF, TGFA
Familial thoracic aortic aneurysm and dissection (TAAD)	KEGG DISEASE	0.0459	MYLK, TGFBR1
Hypomagnesemia	KEGG DISEASE	0.0459	TRPM6, EGF
Multiple epiphyseal dysplasia (MED)	KEGG DISEASE	0.0459	COL9A3, MATN3
Transient neonatal diabetes mellitus (TNDM)	KEGG DISEASE	0.0459	PLAGL1, ZFP57
Non-syndromic autosomal dominant mental retardation	KEGG DISEASE	0.0461	EPB41L1, DOCK8, PACS1, SMARCA4
Cardiac hypertrophy	NHGRI GWAS Catalog	0.0028	PLXNA2, GRIK2, COL17A1, JAG1, SNAP25, BTBD3, SLX4IP
Response to fenofibrate (adiponectin levels)	NHGRI GWAS Catalog	0.0046	OAS2, PMEPA1, SHANK2, SCUBE1, SLC30A4, PCK1
Complement C3 and C4 levels	NHGRI GWAS Catalog	0.0094	HLA, CFHR3, CFH, C3
Neutrophil count	NHGRI GWAS Catalog	0.0119	PLCB4, TGFA, FGGY, PDGFD, PSD3
Nephropathy(idiopathic membranous)	NHGRI GWAS Catalog	0.0137	HLA, ITGB6, PLA2R1
Sleep duration	NHGRI GWAS Catalog	0.0195	PLLP, TMC5, ADAMTS14
Airflow obstruction	NHGRI GWAS Catalog	0.0259	HYKK, LEF1, SERPINB8, GPR126, MAP3K13, PTPRD
Cystic fibrosis severity	NHGRI GWAS Catalog	0.0265	HLA, EHF, AHRR
Metabolite levels (5-HIAA/ MHPG Ratio)	NHGRI GWAS Catalog	0.0265	PIEZO2, ROBO2, ADAM12
Bronchopulmonary dysplasia	NHGRI GWAS Catalog	0.0296	PLXDC2, ZNF770, SPOCK1, TRPS1, RASGRF1, HIVEP3
Major depressive disorder	NHGRI GWAS Catalog	0.0346	PCLO, SLC6A15, ENOX1, SYPL2, IGFBP1, IGFBP3, C12orf5, ATXN1, PIEZO2, TRPS1, RASGEF1B, FGF12, KCNH5
IgA nephropathy	NHGRI GWAS Catalog	0.0346	HLA, ACOXL, TNFSF13
Pulmonary function decline	NHGRI GWAS Catalog	0.0368	MUSK, CSMD1, RORA, FLRT2
Palmitic acid (16:0) plasma levels	NHGRI GWAS Catalog	0.0368	SCD, CNN3, GRIK2, PTPRD
Male-pattern baldness	NHGRI GWAS Catalog	0.0439	AUTS2, EDA2R, AR
Response to citalopram treatment	NHGRI GWAS Catalog	0.0439	LAMA1, RORA, EGFLAM
Hyperlipidemia	FunDO	0.0050	IRS1, CCL5, C3, PAPPA, TXNIP, APOC1, F3, SCD
Thrombocytopenia	FunDO	0.0068	GATA1, CCL5, ITGB3, IL11, CXCL8, MPL
Fibromyalgia	FunDO	0.0126	MAOB, CXCL8, BDNF, IGFBP3
Cirrhosis	FunDO	0.0209	RBP4, KRT18, IGFBP3, KRT8, EGF, F3, FGF2IGFBP1
Hepatitis C	FunDO	0.0321	CD274, CCL5, RBP4, MKI67, CXCL8, KRT18, TLR4, KRT8, FGF2
Thalassemia	FunDO	0.0345	LCN2, CXCL8, ANK2, KIR3DL1, MUC1
Gingival overgrowth	FunDO	0.0417	EDN1, IL15, FGF7
Pulmonary fibrosis	FunDO	0.0474	CSF1, BDNF, MMP7, EDN1, CCL5, ERBB3
Ovary cancer	FunDO	0.0477	LCN2, IL15, CXCL8, FGF7, CASP1
Esophageal tumor	FunDO	0.0477	CD274, TSPAN8, FRAT1, PDCD1LG2, FGF7
Hyperlipidemia	GAD	0.0093	CCL5, HLA, CXCL8, CD22, TNFRSF1B, CD19
Thrombocytopenia	GAD	0.0114	CSMD1, 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
Fibromyalgia	GAD	0.0136	GLI3, 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
Cirrhosis	GAD	0.0204	IRS1, CCL5, ITGB3, NPR1, NPR3, APOC1, LPL
Hepatitis C	GAD	0.0258	DPYD, CELF4, CELF2, FAM117B, TDRKH, LPCAT4, FBLN5, SOBP, PMEPA1, CSMD1, STOX1, CACNB2, CADM1, VEGFC, SLC7A11, LPL, CD109, MCTP2, SLC24A2, PTPRD, ITPK1
Thalassemia	GAD	0.0362	MCTP2, PSD3, CCDC54, ROBO2, ELOVL6
Gingival overgrowth	GAD	0.0419	PLXNA2, ATXN1, IGF2BP2, ABCA13, FN1
Pulmonary fibrosis	GAD	0.0420	CREG2, 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 cancer	GAD	0.0426	CELF4, 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 tumor	GAD	0.048	CACNA2D1, SLC46A3, CHST2, PKDCC, PPID, CDH2

Table 3 Cisplatin resistance pathway and input gene (P < 0.05, FC ≥ 2.0)

Pathway	Input gene	Fold change	Regulation	Genomic coordinates	Cyto band
PI3K-Akt signaling pathway	LAMA1	2.60826	Up	Chr18:6958512-6956742	hs\|18p11.31
	LAMA1	2.75269	Up	Chr18:6942035-6941976	hs\|18p11.31
	GNG4	2.09356	Up	Chr1:235714443-235714384	hs\|1q42.3
	ITGB3	2.96629	Up	Chr17:45389027-45389086	hs\|17q21.32
	ITGB6	7.72783	Up	Chr2:160964233-160958330	hs\|2q24.2
	VEGFC	2.92538	Up	Chr4:177604882-177604823	hs\|4q34.3
	PDGFD	2.42861	Up	Chr11:103778445-103778386	hs\|11q22.3
	IRS1	2.00967	Up	Chr2:227596677-227596618	hs\|2q36.3
	GNGT1	2.04779	Up	Chr7:93536149-93540155	hs\|7q21.3
	CSF1	2.25620	Up	Chr1:110466137-110466196	hs\|1p13.3
	EGF	4.76437	Up	Chr4:110932689-110932748	hs\|4q25
	FGF2	3.02437	Up	Chr4:123819331-123819390	hs\|4q28.1
	FGF2	2.99240	Up	Chr4:123819317-123819376	hs\|4q28.1
	FN1	2.31254	Up	Chr2:216288895-216288217	hs\|2q35
	COL4A6	2.08497	Up	Chrx:107399109-107399050	hs\|Xq22.3
	FGF12	10.99211	Up	Chr3:191860574-191860515	hs\|3q28
	GNG11	2.01984	Up	Chr7:93555764-93555823	hs\|7q21.3
	FGF7	2.19252	Up	Chr15:49776810-49776869	hs\|15q21.2
	LAMA3	2.56116	Down	Chr18:21534735-21534794	hs\|18q11.2
	IFNA21	2.30808	Down	Chr9:21166331-21166272	hs\|9p21.3
	CREB3L3	2.40183	Down	Chr19:4172219-4172278	hs\|19p13.3
	TLR4	2.13271	Down	Chr9:120476856-120476915	hs\|9q33.1
	COL6A2	2.89458	Down	Chr21:47546086-47546145	hs\|21q22.3
	CD19	2.09302	Down	Chr16:28950600-28950659	hs\|16p11.2
	LPAR5	3.83177	Down	Chr12:6728794-6728735	hs\|12p13.31
	COL4A4	2.11177	Down	Chr2:227867523-227867464	hs\|2q36.3
	PCK1	4.49558	Down	Chr20:56141030-56141089	hs\|20q13.31
	VTN	3.82587	Down	Chr17:26694806-26694747	hs\|17q11.2
	GNGT2	16.48365	Down	Chr17:47284034-47283975	hs\|17q21.32
	IL2RG	2.87954	Down	Chrx:70328539-70328480	hs\|Xq13.1
	COL5A3	7.53410	Down	Chr19:10070602-10070543	hs\|19p13.2
	FGF13	17.08866	Down	Chrx:137713947-137713888	hs\|Xq26.3
MAPK signaling pathway	FLNC	4.57879	Down	Chr7:128498538-128498597	hs\|7q32.1
	FLNC	4.81302	Down	Chr7:128498476-128498535	hs\|7q32.1
	CACNB2	7.83293	Down	Chr10:18787305-18787364	hs\|10p12.31
	RASGRF1	4.87152	Down	Chr15:79254554-79254495	hs\|15q25.1
	FOS	2.17501	Down	Chr14:75748214-75748273	hs\|14q24.3
	JUN	2.04000	Down	Chr1:59246570-59246511	hs\|1p32.1
	RASGRP2	3.10358	Down	Chr11:64508971-64508912	hs\|11q13.1
	FGF13	17.08866	Down	Chrx:137713947-137713888	hs\|Xq26.3
	TGFBR1	2.93035	Up	Chr9:101916322-101916381	hs\|9q22.33
	TGFBR1	4.76437	Up	Chr4:110932689-110932748	hs\|4q25
	EGF	4.76437	Up	Chr4:110932689-110932748	hs\|4q25
	FGF12	10.99211	Up	Chr3:191860574-191860515	hs\|3q28
	MAP3K13	2.25019	Up	Chr3:185161379-185165590	hs\|3q27.2
	FGF2	3.02437	Up	Chr4:123819331-123819390	hs\|4q28.1
	FGF2	2.99240	Up	Chr4:123819317-123819376	hs\|4q28.1
	MAP2K7	2.08267	Up	Chr19:7979302-7979361	hs\|19p13.2
	FGF7	2.19252	Up	Chr15:49776810-49776869	hs\|15q21.2
	CACNG4	8.83585	Up	Chr17:65028139-65028198	hs\|17q24.2
	CACNG4	2.94145	Up	Chr17:65029115-65029174	hs\|17q24.2
	CACNB4	2.14311	Up	Chr2:152694239-152694180	hs\|2q23.3
	GADD45A	2.56659	Up	Chr1:68153371-68153430	hs\|1p31.3
	BDNF	2.32411	Up	Chr11:27679959-27679900	hs\|11p14.1
	BDNF	2.30323	Up	Chr11:27677072-27677013	hs\|11p14.1
	CACNA2D1	2.09452	Up	Chr7:81579504-81579445	hs\|7q21.11
Notch signaling pathway	MAML2	2.03379	Up	Chr11:95712434-95712375	hs\|11q21
	JAG1	3.20086	Up	Chr20:10619120-10619061	hs\|20p12.2
	MAML3	2.57919	Up	Chr4:140810806-140810747	hs\|4q31.1
	DTX4	9.99859	Down	Chr11:58975615-58975674	hs\|11q12.1
ErbB signaling pathway	EGF	4.76437	Up	Chr4:110932689-110932748	hs\|4q25
	NRG1	2.77996	Up	Chr8:32474390-32585512	hs\|8p12
	MAP2K7	2.08267	Up	Chr19:7979302-7979361	hs\|19p13.2
	JUN	2.04000	Down	Chr1:59246570-59246511	hs\|1p32.1
	ERBB3	5.29571	Down	Chr12:56482380-56482439	hs\|12q13.2
	ERBB3	8.12050	Down	Chr12:56496160-56496219	hs\|12q13.2
	TGFA	2.37427	Down	Chr2:70675378-70675319	hs\|2p13.3
Jak-STAT signaling pathway	IL11	4.21849	Up	Chr19:55875847-55875788	hs\|19q13.42
	IL15	2.92970	Up	Chr4:142654431-142654490	hs\|4q31.21
	SOCS2	2.00180	Up	Chr12:93969799-93969858	hs\|12q22
	SPRY1	5.95682	Up	Chr4:124324494-124324553	hs\|4q28.1
	LEPR	2.90187	Up	Chr1:66102129-66102188	hs\|1p31.3
	IL2RG	2.87954	Down	Chrx:70328539-70328480	hs\|Xq13.1
	MPL	3.41581	Down	Chr1:43819826-43819885	hs\|1p34.2
NF-kappaB signaling pathway	CXCL2	2.03846	Up	Chr4:74963044-74962985	hs\|4q13.3
	CXCL8	9.97781	Up	Chr4:74609265-74609324	hs\|4q13.3
	TLR4	2.13271	Down	Chr9:120476856-120476915	hs\|9q33.1
HIF-1 signaling pathway	EDN1	2.39081	Up	Chr6:12296672-12296731	hs\|6p24.1
	EDN1	2.46437	Up	Chr6:12296218-12296277	hs\|6p24.1
	EGF	4.76437	Up	Chr4:110932689-110932748	hs\|4q25
	TLR4	2.13271	Down	Chr9:120476856-120476915	hs\|9q33.1
MicroRNAs in cancer	IRS1	2.00967	Up	Chr2:227596677-227596618	hs\|2q36.3
	ZEB2	3.32563	Up	Chr2:145146320-145146261	hs\|2q22.3
	ZEB2	2.70558	Up	Chr2:145182422-145182363	hs\|2q22.3
	CD44	2.02409	Up	Chr11:35253812-35253871	hs\|11p13
	RECK	2.25018	Up	Chr9:36124319-36124378	hs\|9p13.3
	ITGB3	2.96629	Up	Chr17:45389027-45389086	hs\|17q21.32
	SERPINB5	2.61864	Up	Chr18:61172218-61172277	hs\|18q21.33
	GLS	2.36144	Up	Chr2:191829716-191829775	hs\|2q32.2
	GLS	2.07371	Up	Chr2:191827822-191827881	hs\|2q32.2
	ERBB3	5.29571	Down	Chr12:56482380-56482439	hs\|12q13.2
	ERBB3	8.12050	Down	Chr12:56496160-56496219	hs\|12q13.2

Table 4 Dysregulated mRNAs (P < 0.05, FC ≥ 2.0) associated with cisplatin resistance

Gene symbol	P value	FC (abs)	Regulation	Genename	Ref.
FGF7	0.00035	2.19252	Up	Fibroblast growth factor 7	PMID: 22990650
HIPK2	2.63E-06	4.06213	Up	Homeodomain interacting protein kinase 2	PMID: 24846322
EDN1	9.94E-05	2.46437	Up	Endothelin 1	PMID: 21220476
CBS	0.00108	2.29340	Up	Cystathionine-beta-synthase	PMID: 24236104
PDE3B	0.00029	10.44998	Up	Phosphodiesterase 3B, cgmp-inhibited	PMID: 24133626
E2F5	0.00041	2.42888	Up	E2F transcription factor 5, p130-binding	PMID: 22193543
PIN1	0.00104	2.13293	Up	Peptidylprolyl cis/trans isomerase, NIMA-interacting 1	PMID: 26820938
EGF	0.00346	4.76437	Up	Epidermal growth factor	PMID: 27086487
CSF1	0.00025	2.25620	Up	Colony stimulating factor 1 (macrophage)	PMID: 22005523
PCNA	0.00103	2.17028	Up	Proliferating cell nuclear antigen	PMID: 24474685
HIPK2	2.63E-06	4.06213	Up	Homeodomain interacting protein kinase 2	PMID: 24846322
ENTPD6	0.00011	2.43726	Up	Ectonucleoside triphosphate diphosphohydrolase 6 (putative)	PMID: 21519793
AKR1C1	0.00097	2.29646	Up	Aldo-keto reductase family 1, member C1	PMID: 23165153, PMID: 17266043
ASNS	0.00172	2.19491	Up	Asparagine synthetase (glutamine-hydrolyzing)	PMID: 23956056, PMID: 17409444
BDNF	0.00062	2.32411	Up	Brain-derived neurotrophic factor	PMID: 22276165, PMID: 17044982
CABYR	0.01089	2.55664	Up	Calcium binding tyrosine-(Y)-phosphorylation regulated	PMID: 24362251
FGF2	2.15E-06	2.99240	Up	Fibroblast growth factor 2 (basic)	PMID: 12894531
SLC7A11	1.95E-05	2.93256	Up	Solute carrier family 7 member 11	PMID: 24516043
TUBB3	0.00046	2.00213	Up	Tubulin, beta 3 class III	PMID: 25107571
TWIST1	0.00180	2.96340	Up	Twist family bhlh transcription factor 1	PMID: 22673193, PMID: 22245869
JAG1	9.41E-05	3.20086	Up	Jagged 1	PMID: 24659709
ANXA11	0.00031	2.36619	Down	Annexin A11	PMID: 19484149, PMID: 17982121
CCL5	2.67E-05	5.05630	Down	Chemokine (C-C motif) ligand 5	PMID: 26983899
FGF13	0.00044	17.08866	Down	Fibroblast growth factor 13	PMID: 24113164
IGFBP3	7.48E-05	2.92508	Down	Insulin-like growth factor binding protein 3	PMID: 20023704
KLK6	0.00066	2.24596	Down	Kallikrein-related peptidase 6	PMID: 23307575
SLC7A8	4.50E-05	5.36735	Down	Solute carrier family 7 member 8	PMID: 23462296
TGM2	2.88E-05	6.24520	Down	Transglutaminase 2	PMID: 21424127, PMID: 24828664
TLR4	0.00114	2.13271	Down	Toll-like receptor 4	PMID: 21616060, PMID: 22583829
XAF1	0.02405	3.20613	Down	XIAP associated factor 1	PMID: 25824780, PMID: 25240826
TCEA2	0.00061	3.65969	Down	Transcription elongation factor A (SII), 2	PMID: 16142353

Citation: Xie XQ, Zhao QH, Wang H, Gu KS. Dysregulation of mRNA profile in cisplatin-resistant gastric cancer cell line SGC7901. World J Gastroenterol 2017; 23(7): 1189-1202
URL: https://www.wjgnet.com/1007-9327/full/v23/i7/1189.htm
DOI: https://dx.doi.org/10.3748/wjg.v23.i7.1189