Article Figures & Data
Figures
- Fig. 1.
Dendrogram of the top 490 differentially expressed genes distinguishing different histotypes and ovarian surface epithelium. □, ovarian surface epithelium; ▪, serous cancers; ○, clear cell cancers; •, mucinous cancers; ⧫, endometrioid cancers.
- Fig. 2.
Gene expression determined by microarray analysis and semiquantitative RT-PCR for genes up-regulated in mucinous ovarian cancers (TFF1, TFF3, AGR2, TM4SF3, CEACAM6, LGALS4, BCMP11, and CTSE). N, ovarian surface epithelium; C, clear cell; E, endometrioid; S, serous; M, mucinous.
- Fig. 3.
Gene expression determined by microarray analysis and semiquantitative RT-PCR for serous, clear cell, and endometrioid specific genes (AMY2B, RBP4, and FGF9).
Tables
- Table 1.
Clinical characteristics of 50 epithelial ovarian cancer samples
Stage Grade n Serous I 3 6 4 3 III 1 4 3 10 Endometrioid I 2 1 3 1 II 2 1 3 2 III 2 1 3 3 Clear cell I 3 2 II 3 1 III 3 4 IV 3 2 Mucinous I 1 2 2 1 II 2 1 III 1 1 2 1 3 1 IV 2 1 3 1 - Table 2.
Number of genes and ESTs differentially expressed ≥2-fold compared to each individual histotype and with normal ovarian surface epithelial cells
Histotype No. genes/ESTs up-regulated No. genes/ESTs down-regulated Total no. dysregulated genes/ESTs Clear cell 24 1 25 Endometrioid 18 1 19 Serous 5 1 6 Mucinous 55 2 57 - Table 3.
A. Genes 2-fold differentially expressed in mucinous ovarian cancers compared to other histotypes and with normal ovarian surface epithelial cells Symbol Gene description M vs CC M vs E M vs S Av M vs OSE Colon vs OSE Cell growth, differentiation, cell cycle progression, apoptosis, and hormonal regulation TM4SF3 Transmembrane 4 superfamily member 3 8.1 9.0 11.5 9.5 3.0 6.5 SOX2 SRY (sex determining region Y) box 2 8.3 5.9 6.7 7.0 7.1 −1.3 S100P S100 calcium-binding protein P 4.5 7.3 8.9 6.9 10.7 2.6 G0S2 Putative lymphocyte G0/G1 switch gene 2.6 3.6 3.3 3.2 2.0 −3.6 MIG-6 Gene 33/Mig-6 2.4 2.8 3.1 2.8 2.1 −1.1 TM4SF4 Transmembrane 4 superfamily member 4 2.6 2.4 2.4 2.5 2.2 −1.0 CLU Clusterin −2.1 −3.2 −3.7 −3.0 −2.0 −5.9 EMX2 Empty spiracles homologue 2 (Drosophila) −3.1 −4.6 −4.3 −4.0 −3.9 −7.3 Cytoskeletal structure, extracellular matrix formation, cell adhesion, and coagulation AGR2 Anterior gradient 2 (Xenopus laevis) homologue 7.5 7.4 18.1 11.0 15.3 14.2 CEACAM6 Carcinoembryonic antigen-related cell adhesion molecule 6 (nonspecific cross-reacting antigen) 8.0 7.1 8.4 7.8 8.2 6.0 LGALS4 Lectin, galactoside-binding, soluble, 4 (galectin 4) 7.3 6.5 6.8 6.9 6.4 36.5 MMP1 Matrix metalloproteinase 1 (interstitial collagenase) 7.6 4.0 7.7 6.4 10.0 1.2 CEACAM5 Carcinoembryonic antigen–related cell adhesion molecule 5 6.3 6.0 6.5 6.3 5.3 18.4 GAS Gastrin 6.3 5.9 6.0 6.1 5.7 −1.2 BCMP11 Breast cancer membrane protein 11 4.8 4.7 7.1 5.5 3.4 6.4 CLDN18 Claudin 18 4.4 4.3 4.4 4.4 4.6 1.1 TUBB Tubulin, β polypeptide 2.1 3.1 2.9 2.7 4.1 1.8 ANXA10 Annexin A10 2.6 2.5 2.6 2.6 2.2 −1.3 THBS2 Thrombospondin 2 2.2 2.3 2.6 2.4 3.0 −2.6 PLS1 Plastin 1 (I isoform) 2.4 2.3 2.3 2.3 2.5 5.1 EPLIN Epithelial protein lost in neoplasm β 2.2 2.2 2.2 2.2 2.1 2.2 Metabolism, proteolysis, and proteinase inhibition CYP3A5 Cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 5 6.9 4.9 4.2 5.3 3.0 4.2 CTSE Cathepsin E 5.0 5.0 5.0 5.0 4.6 1.4 SERPINE1 Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 3.1 5.5 4.9 4.5 3.5 −2.5 GCNT3 Glucosaminyl (N-acetyl) transferase 3, mucin type 4.9 2.6 5.4 4.3 6.4 12.2 LDLR Low-density lipoprotein receptor (familial hypercholesterolemia) 2.4 2.9 2.4 2.6 3.7 2.4 SERPINB1 Serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 1 2.8 2.2 2.3 2.4 2.9 2.3 RNASE1 RNase A family, 1 (pancreatic) 2.4 2.5 2.1 2.3 3.1 1.6 Protein transport and binding REG4 Regenerating islet-derived family, member 4 8.1 8.4 8.4 8.3 8.8 1.5 SULT1C1 Sulfotransferase family, cytosolic, 1C, member 1 4.6 6.1 4.6 5.1 7.6 1.0 FABP1 Fatty acid–binding protein 1, liver 4.1 4.2 4.3 4.2 4.2 122.8 SDCBP2 Syndecan-binding protein (syntenin) 2 4.7 3.8 3.6 4.0 3.9 15.0 SLC28A2 Solute carrier family 28 (sodium-coupled nucleoside transporter), member 2 2.1 2.1 2.2 2.1 2.0 1.3 EFHD2 EF hand domain containing 2 2.0 2.2 2.0 2.1 2.2 1.7 Immune response and cellular defense TFF1 Trefoil factor 1 (breast cancer, estrogen-inducible sequence expressed in) 12.0 12.7 13.8 12.8 13.2 1.8 TFF3 Trefoil factor 3 (intestinal) 19.9 6.9 10.2 12.3 23.7 45.6 LILRB1 Leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 6.3 6.0 6.9 6.4 4.0 1.2 IL6 Interleukin-6 (IFN, β2) 2.4 7.0 4.7 4.7 6.2 −2.0 RNF128 Ring finger 128 3.4 2.8 6.1 4.1 3.9 4.8 IL8 Interleukin-8 3.6 4.5 3.3 3.8 6.6 −1.4 FCGBP Fc fragment of IgG-binding protein 4.1 3.4 3.5 3.7 3.2 9.4 CXCL12 Stromal cell–derived factor 1 3.3 3.7 3.0 3.3 2.5 1.0 TFF2 Trefoil factor 2 (spasmolytic protein 1) 2.9 3.1 3.3 3.1 2.9 −1.2 MRC1 Mannose receptor, C-type 1 2.5 3.1 3.2 2.9 2.4 1.5 Unknown function PLAC8 Placenta-specific 8 3.5 4.2 4.0 3.9 3.2 10.8 MS4A7 Membrane-spanning 4 domains, subfamily A, member 7 2.2 2.8 2.8 2.6 3.0 1.1 B. Genes 2-fold differentially expressed in endometrioid ovarian cancers compared to other histotypes and with normal ovarian surface epithelial cells (genes with negative fold changes are down-regulated) Symbol Gene description E vs CC E vs S E vs M Av E vs OSE Endometrium vs OSE Cell growth, differentiation, cell cycle progression, apoptosis, and hormonal regulation FGF9 Fibroblast growth factor 9 (glia-activating factor) 5.9 4.3 5.5 5.2 3.2 −1.2 DKK4 Dickkopf homologue 4 (X. laevis) 3.6 3.6 3.1 3.4 3.3 1.3 APCDD1 Adenomatosis polyposis coli down-regulated 1 3.0 3.1 3.6 3.2 2.8 2.6 FZD10 Frizzled (Drosophila) homologue 10 2.4 2.7 2.6 2.6 5.0 1.3 IHH Indian hedgehog homologue 2.6 2.5 2.1 2.4 2.3 1.1 Cytoskeletal structure, extracellular matrix formation, cell adhesion, and coagulation SFN Stratifin 2.2 2.7 2.0 2.3 4.3 1.9 SCGB1D2 Secretoglobin, family 1D, member 2 2.0 2.0 2.6 2.2 2.4 10.4 Metabolism, proteolysis, and proteinase inhibition SERPINA5 Serine (or cysteine) proteinase inhibitor, clade A (α-1 antiproteinase, antitrypsin), member 5 2.5 4.2 4.4 3.7 5.5 5.2 SERPINA1 Serine (or cysteine) proteinase inhibitor, clade A (α-1 antiproteinase, antitrypsin), member 1 3.4 4.0 3.6 3.7 8.4 1.1 GAD1 Glutamate decarboxylase 1 (brain, 67 kDa) 2.6 2.5 2.6 2.6 2.3 1.0 SERPINA3 Serine (or cysteine) proteinase inhibitor, clade A (α-1 antiproteinase, antitrypsin), member 3 2.0 2.3 2.2 2.2 2.0 1.0 Protein transport and binding MT4 Metallothionein IV 3.1 3.4 3.4 3.3 2.8 −1.2 MT1G Metallothionein 1G 4.0 2.2 3.5 3.2 9.1 11.5 Immune response and cellular defense C4BP4 Complement component 4 binding protein, α 3.3 4.4 4.2 4.0 2.9 1.4 CXCL14 Small inducible cytokine subfamily B (Cys-X-Cys), member 14 (BRAK) 2.4 3.5 3.0 3.0 17.0 23.9 C. Genes 2-fold differentially expressed in clear cell ovarian cancers compared to other histotypes and with normal ovarian surface epithelial cells (genes with negative fold changes are down-regulated) Symbol Gene Description CC vs E CC vs S CC vs M Av CC vs OSE Endometrium vs OSE Cell growth, differentiation, cell cycle progression, apoptosis, and hormonal regulation BCAT1 Branched chain aminotransferase 1, cytosolic 4.7 3.1 5.6 4.5 5.0 1.1 CALB1 Calbindin 1 (28 kDa) 3.5 4.5 4.7 4.2 4.7 −1.1 LEFTB Left-right determination, factor B 4.4 2.7 3.0 3.4 4.1 1.2 LGR7 Leucine-rich repeat-containing G protein–coupled receptor 7 2.5 3.1 3.5 3.0 3.1 6.3 Cytoskeletal structure, extracellular matrix formation, cell adhesion, and coagulation PROM1 Prominin-like 1 (mouse) 2.5 3.0 2.9 2.8 10.4 2.8 Metabolism, proteolysis, and proteinase inhibition GALNT11 UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 11 2.9 2.6 3.8 3.1 2.8 1.0 GPX3 Glutathione peroxidase 3 (plasma) 2.6 2.4 2.6 2.5 2.4 2.5 GDA Guanine deaminase 2.1 3.2 2.2 2.5 2.9 2.1 Protein transport and binding ABP1 Amiloride-binding protein 1 [amine oxidase (copper-containing)] 9.6 7.4 4.1 7.0 14.1 1.4 RBP4 Retinol-binding protein 4, plasma 6.2 6.7 3.0 5.3 6.4 2.6 GLRX Glutaredoxin (thioltransferase) 4.8 4.7 3.0 4.2 5.4 1.9 FXYD2 FXYD domain-containing ion transport regulator 2 2.8 2.6 2.9 2.8 2.8 1.0 SLC7A2 Solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 2.6 2.0 2.1 2.2 2.6 2.4 SLC40A1 Solute carrier family 40 (iron-regulated transporter), member 1 −2.0 −2.6 −2.6 −2.4 −4.9 −1.5 Unknown function PHF8 PHD finger protein 8 2.3 2.2 2.3 2.2 2.4 1.6 D. Genes 2-fold differentially expressed in serous ovarian cancers compared to other histotypes and with normal ovarian surface epithelial cells (genes with negative fold changes are down-regulated) Symbol Gene description S vs E S vs CC S vs M Av S vs OSE Fallopian tube vs OSE Cell growth, differentiation, cell cycle progression, apoptosis, and hormonal regulation ID1 Inhibitor of DNA binding 1, dominant-negative helix-loop-helix protein −2.8 −2.5 −2.7 −2.7 −2.4 −1.7 Cytoskeletal structure, extracellular matrix formation, cell adhesion, and coagulation CHI3L1 Chitinase 3–like 1 (cartilage glycoprotein-39) 2.1 3.8 2.7 2.9 3.8 1.5 Metabolism, proteolysis, and proteinase inhibition AMY2B Amylase, α2B; pancreatic 3.4 2.6 3.5 3.2 2.7 4.5 NOTE: Genes with negative fold changes are down-regulated. M, mucinous; S, serous; CC, clear cell; E, endometrioid; OSE, ovarian surface epithelium.
- Table 4.
Ps for the rank-sum analysis to test the correlation between individual histotypes and normal tissues
Normal ovary Fallopian tube Colon Endometrium Clear cell 0.9623 0.7791 0.6775 0.0002 Endometrioid 0.4915 0.5928 0.9748 0.0172 Serous 0.0743 0.0042 0.9993 0.8504 Mucinous 0.6905 0.4863 0.0003 0.9860 NOTE: Bold numbers identify significant correlation at the Ps noted.
September 2005
Volume 11, Issue 17
Volume 11, Issue 17
Patterns of Gene Expression in Different Histotypes of Epithelial Ovarian Cancer Correlate with Those in Normal Fallopian Tube, Endometrium, and Colon
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