Article Figures & Data
Figures
- Fig. 1.
PCA using all of the probe sets (n = 7069). A, the first two PCs are shown. Tumors are annotated with histological type as indicated, and an elliptical region was determined for each histological type such that 95% of samples of a histological type are expected to fall within that region (assuming bivariate normality of the PC scores). B, same scatterplot with samples annotated with histological type and tumor stage (Un, unknown); C, scatterplot with samples annotated with histological type and tumor grade; D, LDA combining information from the first nine PCs, showing separation of clear cell OvCas from all of the other tumor types.
- Fig. 2.
PCA using histological type-specific probe sets (n = 172 probe sets, 158 genes). Scatterplot of the first two PCs computed using the 172 probe sets showing at least 2-fold increased expression in one tumor type compared with each of the others. Individual tumors are annotated with histological type as indicated. Shaded symbols, OvCas with mixed histology.
- Fig. 3.
Comparison of TFF1, FXYD2, and WT1 gene expression from microarray and q-RT-PCR analyses. For each gene, relative expression based on the microarray analysis (A, C, and E) is compared with the mean fold expression (normalized to HPRT1) based on the q-RT-PCR analysis of 10 tumors in each histological group (B, D, and F). Error bars in B, D, and F, SE of the means.
- Fig. 4.
Immunohistochemical analysis of TFF1 and WT1 protein expression in primary OvCas using TMAs. Top row, representative H&E-stained sections of mucinous, endometrioid, clear cell, and serous ovarian adenocarcinomas. Center row, representative sections of primary OvCas immunostained with antibody recognizing TFF1. Bottom row, representative sections of primary OvCas immunostained with antibody recognizing WT1.
Tables
- Table 1
Distribution of OvCas by histological type, FIGO stage, and tumor grade
Type Grade Stage I II III IV U Single differentiation Clear cell, n = 8 3a 3 3 2 Endometroid, n = 33 1 8 1 1 2 5 3 1 1 3 2 2 7 2 Mucinous, n = 10 1 5 1 1 2 1 2 Serous, n = 53 1 3 2 1 1 17 2 3 1 1 21 4 2 Mixed histology Clear cell (serous)b, n = 1 3 1 Endometroid (serous), n = 3 2 1 3 1 1 Serous (endometroid), n = 5 2 1 1 3 1 2 -
a Classified as grade 3, as recommended by the NCCN Practice Guidelines for Ovarian Cancer (8) .
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b Minor component in samples with mixed histology.
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- Table 2
Up-regulated genes expressed at least 2-fold higher (P < 0.01a) in clear cell OvCa compared with other histological types
Gene symbol Mean fold change Ave. Description NCBI locus link Cbvs. M C vs. E C vs. S Stress response GPX3 20.23 15.58 6.78 12.88 Glutathione peroxidase 3 (plasma) 2878 GLRX 5.34 5.97 8.07 6.36 Glutaredoxin (thioltransferase) 2745 LBP 4.20 6.07 6.07 5.37 Lipopolysaccharide-binding protein 3929 CRYAB 4.50 3.51 2.51 3.41 Crystallin, α B 1410 DEFB1 2.53 3.32 4.41 3.33 Defensin, β 1 1672 HCLS1 3.26 3.34 3.39 3.33 Hematopoietic cell-specific Lyn substrate 1 3059 SOD2 3.22 2.79 2.60 2.86 Superoxide dismutase 2, mitochondrial 6648 HSPA2 2.45 2.13 2.60 2.38 Heat shock 70kD protein 2 3306 ORM1 2.33 2.24 2.32 2.30 Orosomucoid 1 5004 Cell proliferation/differentiation, hormones, receptors CSPG2 11.96 13.40 8.73 11.18 Chondroitin sulfate proteoglycan 2 (versican) 1462 IGFBP1 5.84 6.52 7.42 6.57 Insulin-like growth factor binding protein 1 3484 PTHLH 5.95 5.96 7.10 6.31 Parathyroid hormone-like hormone 5744 TCF2 3.91 6.83 8.69 6.15 Transcription factor 2, hepatic; LF-B3 6928 DRIL1 5.40 3.89 5.06 4.74 Dead ringer (Drosophila)-like 1 1820 GPC3 4.05 5.15 4.86 4.66 Glypican 3 2719 IGFBP3 5.06 3.86 5.04 4.62 Insulin-like growth factor binding protein 3 3486 TOB1 2.40 4.31 6.18 4.00 Transducer of ERBB2, 1 10140 MITF 2.80 3.52 4.85 3.63 Microphthalmia-associated transcription factor 4286 NDRG1 3.03 4.37 3.18 3.48 N-myc downstream regulated 10397 NR1H4 2.39 3.61 3.88 3.23 Nuclear receptor subfamily 1, group H, member 4 9971 FGFR3 2.21 3.86 3.70 3.16 Fibroblast growth factor receptor 3 2261 PVR 2.23 3.36 3.53 2.98 Poliovirus receptor 5817 PIG7 2.67 2.97 3.19 2.93 LPS-induced TNF-α factor 9516 IL6 2.47 2.90 2.82 2.72 Interleukin 6 (IFN, β 2) 3569 PTPRM 2.96 2.46 2.63 2.67 Protein tyrosine phosphatase, receptor type, M 5797 FOXO1A 2.01 2.67 2.88 2.49 Forkhead box O1A (rhabdomyosarcoma) 2308 ERBB2 2.40 2.55 2.53 2.49 v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 2064 C5R1 2.03 2.82 2.68 2.48 Complement component 5 receptor 1 (C5a ligand) 728 MIG2 3.05 2.47 2.01 2.48 Mitogen inducible 2 10979 PRX2 2.13 2.43 2.15 2.23 Paired related homeobox protein 51450 Extracellular matrix, cytoskeletal, cell adhesion NID2 4.35 8.56 9.77 7.14 Nidogen 2 22795 LAMB1 3.61 6.27 9.94 6.08 Laminin, β 1 3912 COMP 7.54 6.09 3.99 5.68 Cartilage oligomeric matrix protein (pseudoachondroplasia) 1311 MAGP2 5.02 4.02 2.52 3.70 Microfibril-associated glycoprotein-2 8076 PLS3 2.08 4.83 4.87 3.66 Plastin 3 (T isoform) 5358 MCAM 2.51 3.28 5.57 3.58 Melanoma adhesion molecule 4162 SPP1 6.01 2.83 2.17 3.33 Secreted phosphoprotein 1 (osteopontin, bone sialoprotein I) 6696 LAMC1 3.30 2.76 2.33 2.77 Laminin, γ 1 (formerly LAMB2) 3915 COL4A2 2.72 2.58 2.83 2.71 Collagen, type IV, α 2 1284 E48 2.29 2.69 2.93 2.62 Lymphocyte antigen 6 complex, locus D 8581 PSCDBP 2.44 2.32 2.32 2.36 Pleckstrin homology, Sec7 and coiled/coil domains, binding protein 9595 COL4A1 2.43 2.12 2.53 2.35 Collagen, type IV, α 1 1282 MYOC 2.17 2.21 2.27 2.22 Myocilin, trabecular meshwork inducible glucocorticoid response 4653 Proteases, protease inhibitors, enzyme inhibitors ANXA4 2.11 9.67 12.56 6.36 Annexin A4 307 TFPI2 4.90 4.08 5.90 4.90 Tissue factor pathway inhibitor 2 7980 CST6 3.95 4.10 3.34 3.78 Cystatin E/M 1474 SLPI 3.39 3.49 2.14 2.94 Secretory leukocyte protease inhibitor (antileukoproteinase) 6590 TIMP2 2.23 2.54 2.02 2.25 Tissue inhibitor of metalloproteinase 2 7077 CPM 2.12 2.08 2.29 2.16 Carboxypeptidase M 1368 Metabolism, catabolism GGT1 5.78 6.59 7.23 6.51 Gamma-glutamyltransferase 1 2678 NNMT 7.48 5.62 4.33 5.67 Nicotinamide N-methyltransferase 4837 MAL 10.67 5.86 2.56 5.43 Mal, T-cell differentiation protein 4118 EEF1A2 2.78 4.81 5.09 4.09 Eukaryotic translation elongation factor 1 α 2 1917 HGD 2.44 3.72 6.71 3.93 Homogentisate 1,2-dioxygenase (homogentisate oxidase) 3081 TCN2 3.22 2.88 4.47 3.46 Transcobalamin II; macrocytic anemia 6948 CDA 2.85 3.64 3.77 3.40 Cytidine deaminase 978 PCCA 3.01 2.58 4.85 3.35 Propionyl Coenzyme A carboxylase, α polypeptide 5095 CRYM 2.19 3.19 4.31 3.11 Crystallin, μ 1428 PDXK 3.15 2.70 3.21 3.01 Pyridoxal (pyridoxine, vitamin B6) kinase 8566 CYP1B1 3.26 3.18 2.52 2.96 Cytochrome P450, subfamily I (dioxin-inducible), polypeptide 1 1545 STC1 2.96 2.06 4.25 2.96 Stanniocalcin 1 6781 NP 2.28 2.77 3.99 2.93 Nucleoside phosphorylase 4860 WARS 2.73 2.12 2.40 2.40 Tryptophanyl-tRNA synthetase 7453 HMOX1 2.05 2.15 2.37 2.18 Heme oxygenase (decycling) 1 3162 Transporters, carriers, trafficking FXYD2 18.39 34.43 38.89 29.09 FXYD domain-containing ion transport regulator 2 486 RBP4 14.15 25.51 29.47 22.00 Retinol-binding protein 4, interstitial 5950 SLC6A12 3.31 3.19 2.52 2.99 Solute carrier family 6, member 12 6539 VATI 2.78 2.51 2.48 2.59 Membrane protein of cholinergic synaptic vesicles 10493 GP36B 2.47 2.93 2.15 2.50 Endoplasmic reticulum glycoprotein 10960 RAB9 2.27 2.67 2.53 2.48 RAB9, member RAS oncogene family 9367 KDELR3 2.60 2.44 2.04 2.35 KDEL endoplasmic reticulum protein retention receptor 3 11015 Function not well elucidated C3F 2.40 2.35 2.24 2.33 Putative protein similar to nessy (Drosophila) 10162 ITM2B 2.10 2.11 2.00 2.07 Integral membrane protein 2B 9445 -
a Significance for fold change determined using the Student t test by comparing clear cell samples with all other groups combined.
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b C, clear cell; M, mucinous; E, endometrioid; S, serous; Ave., average; NCBI, National Center for Biotechnology Information.
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Volume 62, Issue 16
