Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis
Tumor Biology
Supplementary Material
YoungSeok Lee1, SunGoo Hwang2, JinKi Kim1, Tae Hwan Park3, Young Rae Kim1, Ho Sung Myeong1, Jong Duck Choi1, Kang Kwon4,CheolSeong Jang2,Young Tae Ro1, Yun Hee Noh1, and Sung Young Kim1
1Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Korea
2Plant Genomics Laboratory, Department of Applied Plant Science, Kangwon National University, Chuncheon, Korea
3Department of Plastic and Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Korea
4School of Korean Medicine, Pusan National University, Pusan, Korea
Address for Correspondence: Sung Young Kim M.D., Ph.D.
Department of Biochemistry, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
E-mail:
Supplementary FigureLegends
Supplementary Fig.S1. General workflow depicting the systematic review of this study.a Selection of microarray datasets for meta-analysis of the acquired lapatinib-resistant breast cancer cell lines, according to Prisma 2009 flow diagram. b The integrated in-silico analysis of DEGs identified by meta-analysis.
Supplementary Fig.S2. Heat-map representation of expression profiles for the top 50 up- and down-regulated DEGs across different datasets.
For visualization of heat-map, individual microarray datasets were re-scaled to prevent the scene from being dominated by study-specific effects. LapS, lapatinib-senstive; LapR, lapatinib-resistant.
Supplementary Fig.S3. The box plot of gene expression value after normalization of RankProd algorithm on INMEX program.
The box plots were generated using the normalized data of 3 parental breast cancer cells and 3 acquired lapatinib-resistant breast cancer cells in individual datasets of microarray. The blue line in each box represents the median of each sample in the individual datasets.
Supplementary Table S1.The top 50 up-regulated genes inthe DEGs identified by meta-analysis.
Entrez ID / Symbol / -Log2 FC / Gene name5954 / RCN1 / +3.11629 / Reticulocalbin 1, EF-hand calcium binding domain
27018 / NGFRAP1 / +2.91857 / Nerve growth factor receptor (TNFRSF16) associated protein 1
5654 / HTRA1 / +2.90237 / HtrA serine peptidase 1
2697 / GJA1 / +2.77331 / Gap junction protein, alpha 1, 43kDa
9510 / ADAMTS1 / +2.75517 / ADAM metallopeptidase with thrombospondin type 1 motif, 1
51186 / WBP5 / +2.75429 / WW domain binding protein 5
84709 / C4orf49 / +2.66848 / Mitochondria-localized glutamic acid-rich protein
2274 / FHL2 / +2.48576 / Four and a half LIM domains 2
9506 / PAGE4 / +2.34541 / P antigen family, member 4 (prostate associated )
129607 / CMPK2 / +2.29592 / Cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial
51316 / PLAC8 / +2.29459 / Placenta-specific 8
4036 / LRP2 / +2.28878 / Low density lipoprotein receptor-related protein 2
64577 / ALDH8A1 / +2.24312 / Aldehyde dehydrogenase 8 family, member A1
7049 / TGFBR3 / +2.22197 / Transforming growth factor, beta receptor III
24147 / FJX1 / +2.02779 / Four jointed box 1 (Drosophila)
6446 / SGK1 / +2.02604 / Serum/glucocorticoid regulated kinase 1
1282 / COL4A1 / +1.99149 / collagen, type IV, alpha 1
84634 / KISS1R / +1.95763 / KISS1 receptor
374918 / IGFL1 / +1.95057 / IGF-like family member 1
3046 / HBE1 / +1.87125 / Hemoglobin, epsilon 1
1284 / COL4A2 / +1.81042 / Collagen, type IV, alpha 2
90737 / PAGE5 / +1.79778 / P antigen family, member 5
389860 / PAGE2B / +1.77172 / P antigen family, member 2B
55214 / LEPREL1 / +1.69491 / Leprecan-like 1
10644 / IGF2BP2 / +1.67796 / Insulin-like growth factor 2 mRNA binding protein 2
11098 / PRSS23 / +1.66016 / Protease, serine, 23
84803 / AGPAT9 / +1.62772 / 1-acylglycerol-3-phosphate O-acyltransferase 9
4147 / MATN2 / +1.57795 / Matrilin 2
84707 / BEX2 / +1.54438 / Brain expressed X-linked 2
85477 / SCIN / +1.52694 / Scinderin
401115 / C4orf48 / +1.49702 / Chromosome 4 open reading frame 48
90843 / TCEAL8 / +1.47025 / Transcription elongation factor A -like 8
284119 / PTRF / +1.36236 / Polymerase I and transcript release factor
84152 / PPP1R1B / +1.32692 / Protein phosphatase 1, regulatory subunit 1B
2745 / GLRX / +1.30252 / Glutaredoxin
3775 / KCNK1 / +1.24053 / Potassium channel, subfamily K, member 1
606 / NBEAP1 / +1.19933 / B-cell CLL/lymphoma 8
8323 / FZD6 / +1.16967 / Frizzled homolog 6
2810 / SFN / +1.16244 / Stratifin
3956 / LGALS1 / +1.13496 / Lectin, galactoside-binding, soluble, 1
55612 / FERMT1 / +1.07155 / Fermitin family homolog 1
145741 / C2CD4A / +1.04799 / Family with sequence similarity 148, member A
51092 / SIDT2 / +1.03392 / SID1 transmembrane family, member 2
7077 / TIMP2 / +0.98685 / TIMP metallopeptidase inhibitor 2
4128 / MAOA / +0.95623 / Monoamine oxidase A
85012 / TCEAL3 / +0.88729 / Transcription elongation factor A -like 3
7076 / TIMP1 / +0.84606 / TIMP metallopeptidase inhibitor 1
4496 / MT1H / +0.74918 / Metallothionein 1H
4495 / MT1G / +0.73074 / Metallothionein 1G
5973 / RENBP / +0.72208 / Renin binding protein
Log2FC = log2 (class1 / class2), FC fold change, class1 lapatinib-sensitive, class2 lapatinib-resistant
Supplementary Table S2.The top 50down-regulated genes inthe DEGs identified by meta-analysis.
Entrez ID / Symbol / -Log2 FC / Gene name6451 / SH3BGRL / -3.08642 / SH3 domain binding glutamate-rich protein like
5304 / PIP / -2.74962 / Prolactin-induced protein
4680 / CEACAM6 / -2.73294 / Carcinoembryonic antigen-related cell adhesion molecule 6
81031 / SLC2A10 / -2.66147 / Solute carrier family 2 (facilitated glucose transporter) member 10
50617 / ATP6V0A4 / -2.42082 / ATPase, H+ transporting, lysosomal V0 subunit a4
90293 / KLHL13 / -2.31248 / Kelch-like family member 13
10140 / TOB1 / -1.77651 / Transducer of ERBB2, 1
54847 / SIDT1 / -1.72621 / SID1 transmembrane family, member 1
1290 / COL5A2 / -1.67278 / Collagen, type V, alpha 2
1545 / CYP1B1 / -1.57364 / Cytochrome P450, family 1, subfamily B, polypeptide 1
79161 / C7orf23 / -1.54334 / Transmembrane protein 243, mitochondrial
1917 / EEF1A2 / -1.51851 / Eukaryotic translation elongation factor 1 alpha 2
1573 / CYP2J2 / -1.51370 / Cytochrome P450, family 2, subfamily J, polypeptide 2
8309 / ACOX2 / -1.39153 / Acyl-CoA oxidase 2, branched chain
828 / CAPS / -1.26861 / Calcyphosine
4071 / TM4SF1 / -1.21370 / Transmembrane 4 L six family member 1
3017 / HIST1H2BD / -1.20881 / Histone cluster 1, H2bd
64288 / ZNF323 / -1.20543 / Zinc finger and SCAN domain containing 31
3488 / IGFBP5 / -1.19205 / Insulin-like growth factor binding protein 5
81831 / NETO2 / -1.15798 / Neuropilin (NRP) and tolloid (TLL)-like 2
1021 / CDK6 / -1.09905 / Cyclin-dependent kinase 6
51101 / ZC2HC1A / -1.04892 / Family with sequence similarity 164, member A
4246 / SCGB2A1 / -0.21928 / Secretoglobin, family 2A, member 1
306 / ANXA3 / -0.04402 / Annexin A3
55752 / SEPT11 / -0.76067 / Septin 11
139221 / MUM1L1 / -1.16390 / Melanoma associated antigen 1-like 1
214 / ALCAM / -1.22987 / Activated leukocyte cell adhesion molecule
253190 / SERHL2 / -2.23807 / Serine hydrolase-like 2
51292 / GMPR2 / -1.31257 / Guanosine monophosphate reductase 2
387914 / SHISA2 / -1.35112 / Shisa homolog 2
79258 / MMEL1 / -1.62063 / Membrane metallo-endopeptidase-like 1
8345 / HIST1H2BH / -1.28126 / Histone cluster 1, H2bh
11151 / CORO1A / -1.03205 / Coronin, actin binding protein, 1A
7205 / TRIP6 / -1.25333 / Thyroid hormone receptor interactor 6
91523 / FAM113B / -1.54532 / Family with sequence similarity 113, member B
10202 / DHRS2 / -1.43310 / Dehydrogenase/reductase member 2
8835 / SOCS2 / -0.15734 / Suppressor of cytokine signaling 2
55711 / FAR2 / -2.16029 / Fatty acyl CoA reductase 2
7474 / WNT5A / -2.19610 / Wingless-type MMTV integration site family, member 5A
199974 / CYP4Z1 / -2.37226 / Cytochrome P450, family 4, subfamily Z, polypeptide 1
7054 / TH / -1.87871 / Tyrosine hydroxylase
1829 / DSG2 / -1.18813 / Desmoglein 2
26996 / GPR160 / -2.41078 / G protein-coupled receptor 160
5266 / PI3 / -0.56189 / Peptidase inhibitor 3, skin-derived
23022 / PALLD / -0.58810 / Palladin, cytoskeletal associated protein
57544 / TXNDC16 / -1.59282 / Thioredoxin domain containing 16
1535 / CYBA / -1.04175 / Cytochrome b-245, alpha polypeptide
55638 / SYBU / -1.61962 / Syntabulin
10565 / ARFGEF1 / -1.24679 / ADP-ribosylation factor guanine nucleotide-exchange factor 1
9022 / CLIC3 / -1.16375 / Chloride intracellular channel 3
Log2FC = log2 (class1 / class2), FC fold change, class1 lapatinib-sensitive, class2 lapatinib-resistant
Supplementary Fig.S1. General workflow depicting the systematic review of this study.
Supplementary Fig.S2. Heat-map representation of expression profiles for the top 50 up- and down-regulated DEGs across different datasets.
Supplementary Fig.S3. The box plot of gene expression value after normalization of RankProd algorithm on INMEX program.