Article Figures & Data
Figures
- Fig. 1.
Global gene expression analysis. A, scatterplots of IOSE versus ML10, OVT6 (ovarian), and Tu98 (colon) generated using the Spotfire Pro 4.0 software (Cambridge, MA). The tag frequency for each tag (per 100,000) is plotted on a logarithmic scale for the indicated libraries. B, Pearson correlation coefficients were calculated for each pairwise comparison of the 16 ovarian and colon SAGE libraries. C, dendrograms were created from hierarchical cluster analysis (18) of all colon and ovarian SAGE libraries (left), ovarian samples only (middle), and nonmalignant ovarian and colon epithelia as well as ovarian and colon primary tumors (right). Normalized values for the 10,000 most highly expressed genes in each library were used for all manipulations.
- Fig. 2.
Immunohistochemical staining of serous carcinomas. A–F, two representative cases are illustrated. A–C, case 1. Sections are stained as follows: A, H&E; B, Ep-CAM; and C, ApoJ. Tumor cells show strong, diffuse membrane staining for Ep-CAM and diffuse cytoplasmic staining for ApoJ. D–F, case 2. Sections as stained as follows: D, H&E; E, Ep-CAM; and F, ApoJ. Tumor implant on ovarian surface shows strong, diffuse membrane staining for Ep-CAM in tumor cells, whereas adjacent OSE is negative. ApoJ expression is more focal than in case 1 and localizes to the luminal aspect of tumor cells. G–I, staining patterns of claudin-3 and -4. Claudin-4 shows strong membrane staining on tumor cells. Adjacent detached normal epithelium (G) is negative. Claudin-3 shows predominantly membrane staining in the tumor illustrated in H and shows both cytoplasmic and membrane staining in the tumor in I. Overlying mesothelium in I is negative.
Tables
- Table 1
Summary of SAGE library analyses
Librarya Sequence Tagsb Unique tagsc Genesd ≥2 tagse HOSE 2,290 47,881 16,034 12,778 4,532 IOSE 1,912 47,549 18,004 14,771 5,681 ML10 1,935 55,700 18,727 14,939 6,637 OVT6 2,104 41,620 18,476 15,646 4,799 OVT7 2,089 53,898 19,523 15,858 5,669 OVT8 2,076 32,494 16,363 14,153 3,815 OV1063 2,146 37,862 15,231 12,656 4,746 A2780 1,332 21,587 10,717 9,249 2,761 ES-2 1,775 35,352 14,739 12,335 3,952 POOL 2,201 10,554 5,956 5,238 1,627 Total 19,860 384,497 82,533 56,387 28,219 -
a The libraries are: HOSE, human ovarian surface epithelium from short-term culture; IOSE, SV40-immortalized ovarian surface epithelium; ML10, SV40-immortalized benign cystadenoma; OVT6, OVT7, and OVT8, primary ovarian serous adenocarcinomas; OV1063, A2780, and ES2, ovarian cancer cell lines; POOL, a pool of 10 ovarian cancer cell lines.
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b Tag numbers after elimination of linker-based tags and duplicate ditags.
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c Number of unique tags identified in each library.
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d Number of genes identified after correction for sequencing errors.
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e Number of genes represented at least twice.
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- Table 2
Subsets of genes identified in the ovarian and colon SAGE librariesa
Gene Product HOSEb IOSE ML10 A2780 ES-2 OV1063 POOL OVT6 OVT7 OVT8 NC1 NC2 SW837 HCT116 Tu102 Tu98 Keratin 8 86 383 4 5 20 195 28 53 135 71 1436 939 418 57 261 295 Keratin 18 21 490 93 0 28 151 85 43 89 25 281 127 360 68 142 104 Keratin 19 96 2 32 0 0 53 38 46 54 114 398 178 145 35 30 100 Keratin 17 0 0 0 0 0 0 38 10 11 6 0 0 5 0 5 4 Keratin 16 4 6 9 5 17 11 19 0 11 15 0 6 18 8 9 8 Keratin 10 19 0 7 5 17 5 0 0 6 3 2 4 0 3 0 4 Keratin hHb3 0 2 0 0 79 0 0 0 7 0 0 0 0 2 0 0 Keratin K5 0 0 0 0 3 0 0 2 4 18 0 0 3 0 0 0 Vimentin 169 124 185 208 390 8 0 106 32 68 0 0 0 0 4 2 Keratin 20 0 0 0 0 0 0 0 0 0 0 207 121 2 0 5 12 Keratin 7 102 48 5 0 25 441 28 84 41 65 2 2 2 0 0 4 CEA 0 0 0 0 0 0 0 0 0 0 273 174 3 0 34 87 Cadherin-6 17 6 9 0 6 16 0 12 2 0 8 12 40 15 0 8 N-Cadherin 2 15 11 0 0 5 0 2 2 3 0 2 0 0 2 0 Cadherin-13 0 0 6 0 0 0 0 0 0 0 0 0 0 0 0 0 Cadherin-11 2 0 5 0 0 0 0 5 0 0 0 0 0 0 0 0 Cadherin-43 8 8 5 0 3 3 0 5 6 6 0 0 0 0 0 4 E-Cadherin 0 0 0 0 0 24 0 2 13 6 84 72 8 3 18 50 VE-Cadherin 6 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 LI-Cadherin 0 0 0 0 0 0 0 0 0 0 38 29 2 0 12 12 -
a All libraries were normalized to tag number per 100,000.
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b HOSE, normal human ovarian surface epithelium; IOSE, SV40-immortalized normal human ovarian surface epithelium; ML10, SV40-immortalized benign cystadenoma; A2780, ES-2, OV1063, and POOL, ovarian cancer cell lines; OVT6, OVT7, and OVT8, ovarian cancer primary tumors; NC1 and NC2, normal colon epithelia; SW837 and HCT116, colon cancer cell lines; Tu102 and Tu98, colon cancer primary tumors.
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- Table 3
Subset of genes differentially expressed in ovarian tumors compared with nonmalignant ovarian samples
Tag Gene Expressiona Function Fold OSE ML10 Ovarian tumors Colon epithelium Colon tumors Up-regulatedb GGGCATCTCT HLA-DR α chain 289 − ++ − − MHC, class II/antigen presentation TTTGGGCCTA Cysteine-rich protein 1 123 − ++ + − LIM/double zinc finger ATCGTGGCGG Claudin 4 109 − + ++ + Tight junction barrier function TATTATGGTA ESTs 101 − + − − Unknownc GCCTACCCGA Surface marker 1/GA733-1/TROP2 93 − + − − Tumor Agc/Ca2+ CTCGCGCTGG Claudin 3 83 − + ++ + Tight junction barrier function TTGCTTGCCA Ceruloplasmin (ferroxidase) 79 − + − − Secreted metalloprotein/antioxidant CCTGCTTGTC HE4 72 − ++ + − Secreted protease inhibitor AGGGAGGGGC Glutathione peroxidase 3 (plasma) 69 − + − − Secreted selenoprotein/peroxidase TGTGGGAAAT Secretory leukocyte protease inhibitor 60 − ++ − − Secreted serine protease inhibitor CCTGATCTGC ESTs 56 − + − − Unknown ACCATTGGAT IFN-induced transmembrane protein 1 49 − ++ − + Receptor for IFN signaling AGTTTGTTAG Ep-CAM/EGP2/TROP1/GA733-2 48 − + ++ + Tumor Ag/Ca-independent CAM/proliferation CCTGGGAAGT Mucin 1 43 − ++ + + Tumor Ag/type-I membrane glycoprotein CAACTAATTC ApoJ/clusterin 39 − ++ − − Secreted chaperone/cytoprotection GCCTGCAGTC Serine protease inhibitor, Kunitz type 2 34 − ++ ++ + Transmembrane/protease inhibitor CGACCCCACG ApoE 34 − ++ − − Lipoprotein particle binding, internalization, and catabolism TTCTGTGCTG Complement component 1, r subcomponent 24 − + − − Serine protease of complement system/autoimmune diseases CGCCGACGAT G1P3/IFI-6-16 24 − ++ + + IFN primary response/α-IFN-inducible CCCGCCCCCG Lutheran blood group protein/BCAM 17 − ++ − − Possible cell surface receptor/immunoglobulin superfamily GATCAGGCCA Unknown 16 − ++ − + Unknown GTGGAAGACG Mal 16 − + − − Trans-Golgi membrane protein (epithelial cells)/T-cell differentiation GATGAGGAGA ESTs 13 + ++ − + Unknown TTCCCTTCTT HLA-DPB1 13 − + − − MHC, class II/antigen presentation CCCCCTGCAG Mesothelin 12 − ++ − − GPI-anchored/mesothelioma and ovarian cancer antigen/cell adhesion TGCTGCCTGT Bone marrow stroma antigen 2/BST-2 12 − ++ − + Type II transmembrane protein/pre-B-cell growth TGCAGCACGA HLA-Cw 10 − ++ ++ + MHC, class I/antigen presentation Down-regulatedd GGTTATTTTG Unknown 99 + − − − Unknown TGTCATCACA Lysyl oxidase-like 2 73 + − − − Secreted/collagen and elastin cross-linker AAAATAAACA Chloride intracellular channel 4 like 29 + − − − Ion transport TAAAAATGTT Plasminogen activator inhibitor, type 1 26 ++ − − − Serine protease inhibitor family/tPA inhibitor GAGCTTTTGA EST 14 + − − − Unknown GGCTGATGTG Glycine t-RNA synthetase 13 + − − − Protein synthesis CGACGAGGAG Epithelial membrane protein-3 13 + − − − Proliferation, differentiation, and apoptosis GCCCCCAATA Galectin-1 10 ++ + − − β-Galactoside binding lectin/ECM interaction and proliferation GCAACTTGGA Vinexin β 10 + − − − Cell adhesion and cytoarchitecture -
a Expression is defined as: −, 0–9 tags/100,000; +, 10–49 tags/100,000; ++, >49 tags/100,000.
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b Candidates up-regulated at least 30-fold in tumors.
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c Ag, antigen; CAM, cellular adhesion molecule; BCAM, basal cell adhesion molecule; GPI, glycosylphosphatidyl inositol; tPA, tissue plasminogen activator; ECM, extracellular matrix. IFN, interferon.
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d Candidates down-regulated at least 10-fold in tumors.
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Volume 60, Issue 22
