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Results for “expression profiling”

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PubMed2003

Expression profile of trophoblast invasion-associated genes in the pre-eclamptic placenta.

The primary pathology of pre-eclampsia is thought be a defect in placentation due to failure of trophoblast invasion. Here, we aim to identify the expression profile of invasion-associated genes in the pre-eclamptic placenta. Messenger RNA (mRNA) expression levels of extracellular matrix molecule-related genes in five pre-eclamptic placentas and in five strictly matched normal placentas were assayed using complementary DNA (cDNA) microarrays representing over 220 human cytokine-associated or hormone-associated genes. Results demonstrated greater than two-fold higher expression of 18 extracellular matrix molecule genes, including cadherin, collagen, integrin and selectin, in the pre-eclamptic placenta. Extracellular matrix molecule degradation-related genes, including matrix metalloproteinase (MMP)-10, MMP-13, MMP-15, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-3, plasminogen and plasminogen activator, were also highly expressed in the pre-eclamptic placenta, compared to the normal placenta. Results suggest that the abnormal expression profiles of extracellular matrix molecules and degrading proteinases might be associated with the pathogenesis of pre-eclampsia.

Adult↗

PubMed2002

Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles.

Acute myeloid leukemia (AML) is a heterogeneous group of genetically defined diseases. Their classification is important with regard to prognosis and treatment. We performed microarray analyses for gene expression profiling on bone marrow samples of 37 patients with newly diagnosed AML. All cases had either of the distinct subtypes AML M2 with t(8;21), AML M3 or M3v with t(15;17), or AML M4eo with inv(16). Diagnosis was established by cytomorphology, cytogenetics, fluorescence in situ hybridization, and reverse transcriptase-PCR in every sample. By using two different strategies for microarray data analyses, this study revealed a unique correlation between AML-specific cytogenetic aberrations and gene expression profiles.

Acute Disease↗

PubMed2003

Gene expression profile of cardiomyocytes in hypertrophic heart induced by continuous norepinephrine infusion in the rats.

Catecholamines play an important role in the development of cardiac hypertrophy. To observe cardiomyocyte-specific gene expression changes induced by catecholamines in vivo, left ventricular cardiomyocytes were isolated from male Sprague-Dawley rats after continuous infusion of norepinephrine (NE; 0.2 mg/kg per hour intravenously) for 0.5, 1, 2, 3 and 7 days. The gene expression profiles of these cells during different NE infusion stages were assessed by using a cDNA microarray, and the microarray data were further analyzed by a clustering method. Cardiac hypertrophy was induced upon continuous NE infusion, with the peak at 3 days. Meanwhile, manifest changes in gene expression profile within cardiomyocytes over the time course were revealed, most of the genes never having been reported to be involved in cardiac hypertrophy. The number of genes displaying differential expression also peaked at the middle stage of infusion (2-3 days), and the majority of the signaling molecules were found differentially expressed mainly at this stage, including phosphatidylinositol 3-kinase, calcium/calmodulin-dependent protein kinase II and non-receptor tyrosine kinases, etc. The tumor suppressor p53 was found up-regulated at very early (0.5 days) and late stages (7 days) of NE infusion. Self-organization clustering analysis revealed subsets of coordinate regulated genes. One set consisted of several enzymes involved in energy metabolism, including carnitine octanoyltransferase, ATP synthase subunit c, pancreatic lipase and glycogen phosphorylase, possessing a similar expression pattern with a rapidly elevated expression level at the early stage of NE infusion. This is the first study to provide transcriptional information for cardiomyocytes, a single cell type, in the heart during the development of cardiac hypertrophy in vivo, and may provide accurate clues to elaborate hypotheses about the evolution of this pathology.

Animals↗

PubMed2006

Expression profiling defines a recurrence signature in lung squamous cell carcinoma.

Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is approximately 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumor gene expression for a total of 51 SCCs (Stages I-III) on 22 323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 71-gene signature capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for cancer-related death. These two signatures were pooled to generate a 111-gene signature which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of 58 (Stages I-III SCCs). This signature also predicted differences in survival [log-rank P=0.0008; hazard ratio (HR), 3.8; 95% confidence interval (CI), 1.6-8.7], and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene-expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool.

Aged↗

PubMed2005

Characterization of the genomic structures and selective expression profiles of nine class I small heat shock protein genes clustered on two chromosomes in rice (Oryza sativa L.).

The cytosolic class I small heat shock proteins (sHSP-CI) represent the most abundant sHSP in plants. Here, we report the characterization and the expression profile of nine members of the sHSP-CI gene family in rice (Oryza sativa Tainung No.67), of which Oshsp16.9A, Oshsp16.9B, Oshsp16.9C, Oshsp16.9D and Oshsp17.9B are clustered on chromosome 1, and Oshsp17.3, Oshsp17.7, Oshsp17.9A and Oshsp18.0 are clustered on chromosome 3. Oshsp17.3 and Oshsp18.0 are linked by a 356-bp putative bi-directional promoter. Individual gene products were identified from the protein subunits of a heat shock complex (HSC) and from in vitro transcription/ translation products by two-dimensional gel electrophoreses (2-DE). All sHSP-CI genes except Oshsp17.9B were induced strongly after a 2-h heat shock treatment. The genes on chromosome 3 were induced rapidly at 32 and 41 degrees C, whereas those on chromosome 1 were induced slowly by similar conditions. Seven of these genes, except Oshsp16.9D and Oshsp17.9B, were induced by arsenite (As), but only genes on chromosome 3 were strongly induced by azetidine-2-carboxylic acid (Aze, a proline analog) and cadmium (Cd). A similar expression profile of all sHSP-CI genes at a lower level was evoked by ethanol, H2O2 and CuCl2 treatments. Transient expression assays of the promoter activity by linking to GUS reporter gene also supported the in vivo selective expression of the sHSP-CI genes by Aze treatment indicating the differential induction of rice sHSP-CI genes is most likely regulated at the transcriptional level. Only Oshsp16.9A abundantly accumulated in mature dry seed also suggested additionally prominent roles played by this HSP in development.

Azetidinecarboxylic Acid↗

PubMed2004

Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome.

Pheochromocytomas in von Hippel-Lindau (VHL) syndrome produce exclusively norepinephrine, whereas those in multiple endocrine neoplasia type 2 (MEN 2) produce epinephrine. This study examined the pathways activated in VHL-associated pheochromocytomas by comparing gene expression profiles in VHL and MEN 2 tumors in relationship to profiles in sporadic norepinephrine- and epinephrine-producing tumors. Larger and more distinct differences in gene expression among hereditary than sporadic tumors indicated the importance of the underlying mutation to gene expression profiles. Many of the genes over-expressed in VHL compared with MEN 2 tumors were clearly linked to the hypoxia-driven angiogenic pathways that are activated in VHL-associated tumorigenesis. Such genes included those for the glucose transporter, vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 2, tie-1, VEGF receptor 2 and its coreceptor, neuropilin-1. Other up-regulated genes, such as connective tissue growth factor, cysteine-rich 61, matrix metalloproteinase 1, vascular endothelial cadherin, tenascin C, stanniocalcin 1, and cyclooxygenases 1 and 2 are known to be involved in VEGF-regulated angiogenesis. Shared differences in expression of subsets of genes in norepinephrine- versus epinephrine-producing hereditary and sporadic pheochromocytomas indicated other differences in gene expression that may underlie the biochemical phenotype. Over-expression of the hypoxia-inducible transcription factor, HIF-2alpha, in norepinephrine-predominant sporadic and VHL tumors compared with epinephrine-producing tumors indicates that expression of this gene depends on the noradrenergic biochemical phenotype. The findings fit with the known expression of HIF-2alpha in norepinephrine-producing cells of the sympathetic nervous system and might explain both the development and noradrenergic biochemical phenotype of pheochromocytomas in VHL syndrome.

Adolescent↗

PubMed2000

Expression profiling of pancreatic beta cells: glucose regulation of secretory and metabolic pathway genes.

Pancreatic beta cells respond to changes in blood glucose by secreting insulin and increasing insulin synthesis. To identify genes used in these responses, we have carried out expression profiling of beta cells exposed to high (25 mM) or low (5.5 mM) glucose by using oligonucleotide microarrays. Functional clustering of genes that averaged a 2.2-fold or greater change revealed large groups of secretory pathway components, enzymes of intermediary metabolism, cell-signaling components, and transcription factors. Many secretory pathway genes were up-regulated in high glucose, including seven members of the endoplasmic reticulum (ER) translocon. In agreement with array analysis, protein levels of translocon components were increased by high glucose. Most dramatically, the alpha subunit of the signal recognition particle receptor was increased over 20-fold. These data indicate that the translocon and ribosome docking are major regulatory targets of glucose in the beta cell. Analysis of genes encoding enzymes of intermediary metabolism indicated that low glucose brought about greater utilization of amino acids as an energy source. This conclusion was supported by observations of increased urea production under low-glucose conditions. The above results demonstrate genome-wide integration of beta-cell functions at the level of transcript abundance and validate the efficacy of expression profiling in identifying genes involved in the beta-cell glucose response.

Animals↗

PubMed2006

Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.

Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.

Apoptosis↗

PubMed2006

Strategies for comparing gene expression profiles from different microarray platforms: application to a case-control experiment.

Meta-analysis of microarray data is increasingly important, considering both the availability of multiple platforms using disparate technologies and the accumulation in public repositories of data sets from different laboratories. We addressed the issue of comparing gene expression profiles from two microarray platforms by devising a standardized investigative strategy. We tested this procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with resveratrol. Gene expression profiles were obtained using high-density, short-oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and CodeLink (Amersham). Interplatform analyses were carried out on 8414 common transcripts represented on both platforms, as identified by LocusLink ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink features, respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both platforms. Multiple analyses (BLAST alignment of probes with target sequences, gene ontology, literature mining, and quantitative real-time PCR) permitted us to investigate the factors contributing to the generation of platform-dependent results in single-color microarray experiments. An effective approach to cross-platform comparison involves microarrays of similar technologies, samples prepared by identical methods, and a standardized battery of bioinformatic and statistical analyses.

Breast Neoplasms↗

PubMed2005

Gene expression profiles of peripheral and cord blood mononuclear cells altered by thymic stromal lymphopoietin.

Thymic stromal lymphopoietin (TSLP) was reported to induce dendritic cells to produce Th2-attracting chemokines, followed by allergic inflammation through stimulating not only CD4-positive T cells but also CD8-positive T cells. Therefore, in this experiment, GeneChip and hierarchical clustering were applied to screen the molecules in whole immunity triggered by TSLP directly and indirectly using both adult peripheral and cord blood mononuclear cells as well as isolated monocytes. Gene expression profiles screened a variety of molecules that are triggered by TSLP with or without CD40 ligation. In the profile, RNA expressions of indoleamine 2,3-dioxygenase, that is known to induce anergy of T cells and natural killer cells in protecting fetal rejection; many kinds of proteasomes that were reported to trigger cytokine production by inhibiting suppressors of NF-kappaB; and several kinds of chemokines increased, whereas RNA expression of superoxide dismutase 1 decreased, which was unexpected but considered worthy of notice. Expression of chemokines at protein levels and enzymatic activity of indoleamine 2,3-dioxygenase was further confirmed to increase in the presence of TSLP using ELISA and HPLC, respectively. These results suggest that the advent of microarray technology may enable us to screen novel molecular targets to treat TSLP-related allergic inflammation.

Adult↗

PubMed2001

Gene expression profiling in human esophageal cancers using cDNA microarray.

Human esophageal cancer cell lines and human esophageal cancer tissues were profiled on cDNA microarrays. In esophageal cancer cell lines, KYAE and OE-33 (adenocarcinomas) were distinguished from KYSE series (squamous cell carcinomas). Although SK-GT-4 and TE7 were derived from adenocarcinomas, they had a comparatively similar expression profile to the KYSE series. A set of genes whose expression commonly either increased or decreased in cancer cell lines was identified. Genes that were characteristically expressed in KYAE and OE-33 were also identified. The gene expression profiles of cancer tissues (CTs) were remarkably different from those of the cancer cell lines (CCLs). Notable differences between CCLs and CTs were observed in matrix metalloproteinases, plasminogen activator, collagens, paxillin, and thrombospondin 2, etc., whose expression was not increased in CCLs but increased in CTs. Twenty-three genes were extracted to categorize patients according to their prognoses, and clustering analyses, using these genes, were performed successfully.

Adenocarcinoma↗

PubMed2006

Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma.

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. We identified 257 genes that were commonly up-regulated and 721 genes that were down-regulated in RCCs. None of top 24 up-regulated genes that showed most significant differences in informative RCC-cases were included in previous reports describing expression profiles of RCC using RNAs isolated from bulk tissues. These findings suggest that it is important to purify as much as possible the populations of cancerous and normal epithelial cells obtained from surgical specimens. Among the significantly-transactivated genes, we focused on Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small-interfering RNA (siRNA). Effective down-regulation of its expression levels in RCC cells significantly attenuated RCC cell viability. In conclusion, our data should be helpful for a better understanding of the tumorigenesis of RCC and should contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with RCC.

Adult↗

PubMed2002

Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi.

We used microarray analysis to investigate expression profiles of 589 known genes committed to cell growth control to characterize regulatory circuitry for cell proliferation in complete moles (CMs). CMs are characterized by hyperplastic trophoblast and have a high propensity to give rise to choriocarcinoma. Characteristic alterations in gene expression profiles were observed when compared with normal villi. Fifty-seven genes were significantly up-regulated in CMs and involved the Ras-Map kinase 3, Jak-STAT5, and Wnt signal pathways, implicating growth factor or cytokine-mediated signal pathways in the trophoblastic hyperplasia of CMs. Several genes associated with anti-apoptosis, cell structuring, and/or cell attachment were also up-regulated in CMs. In contrast, relatively fewer genes were down-regulated and these involved IGFBPs, versican, interleukin-1, tumor necrosis factor receptor, CD44, and RAD52. Genes identified in this study may elucidate regulation mechanisms of trophoblastic proliferation and mechanisms causing a pathological phenotype in CMs.

Apoptosis↗

PubMed2004

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography.

PURPOSE: 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18F-FDG uptake have more aggressive biological potential than those with low uptake. METHODS: Surgical specimens were obtained from ten patients with HCC (six males and four females, age range 38-68 years). The tumour samples were divided into two groups based on the 18F-FDG PET scan findings: high 18F-FDG uptake (n=4) and low 18F-FDG uptake (n=6). RESULTS: The pathological tumour grade was closely correlated with the 18F-FDG uptake pattern: HCCs with high 18F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18F-FDG uptake showed increased expression of 11 genes--including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose:N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor--compared to those with low uptake (p<0.005). Nine genes, including regulator of mitotic spindle assembly 1, grb2-related adaptor protein and beta-1,3-n-acetylglucosaminyltransferase, were repressed. CONCLUSION: Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Adult↗

PubMed2004

Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas.

The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of an associated invasive carcinoma in IPMNs. Using oligonucleotide microarrays, we performed a large-scale gene expression profiling of 12 IPMNs with or without an associated invasive carcinoma. A subset of genes identified was validated for the gene expression patterns in a large panel of IPMNs by reverse-transcription polymerase chain reaction and/or immunohistochemistry. A total of 673 transcripts were identified as expressed at significantly higher levels (P < 0.05 and at fivefold or greater) in IPMNs relative to normal pancreatic ductal epithelial samples. Of interest, many of the genes identified as overexpressed in IPMNs have also been previously reported to be highly expressed in infiltrating ductal adenocarcinoma of the pancreas. By analyzing genes overexpressed selectively in IPMNs with an associated invasive carcinoma (n = 7), we also identified a panel of genes potentially associated with the invasive phenotype of the neoplasms. Immunohistochemical validation revealed that claudin 4, CXCR4, S100A4, and mesothelin were expressed at significantly high frequency in invasive IPMNs than in noninvasive IPMNs. Notably, the expression of at least two of the four proteins was observed in 73% of 22 invasive IPMNs but in none of 16 noninvasive IPMNs (P < 0.0001). Our findings suggest that preoperative assessment of gene expression profiles may be able to differentiate invasive from noninvasive IPMNs.

Adenocarcinoma, Mucinous↗

PubMed2003

Analysis of costimulation by 4-1BBL, CD40L, and B7 in graft rejection by gene expression profiles.

Recent studies affirm costimulatory blockade as a beneficial means of preventing allograft rejection. The precise molecular effects of these pathways, however, are not entirely understood. A striking example is in the costimulatory pathways, 4-1BB/4-1BBL, CD40/CD40L, and B7/CD28. Blocking any one of these prolongs graft survival, yet each operates via distinct immunomodulatory signals. To examine the mechanistic relationships among these signals, our approach was a comprehensive investigation of their molecular constituents. Using a model of heterotopic heart transplantation in mice with a costimulatory pathway deficiency, we analyzed the expression profiles of a large panel of immune and inflammatory genes using ribonuclease protection assays coupled with algorithms. We found that while graft survival was prolonged in all groups, each pathway modulates a unique profile of expressed genes. There were 19 genes, for example, with significant changes in expression compared to the control, yet none of these were similarly modulated in all three groups. Our study reveals that despite similar delays of allograft rejection, the molecular basis for this effect is distinct in all three costimulatory pathways. Furthermore, we underscore the existence of numerous molecular mechanisms affecting graft survival. This, in turn, provides crucial implications for clinical treatment post-transplant where inhibitors would be designed to target multiple mechanisms.

4-1BB Ligand↗

PubMed2005

Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma.

AIMS: To compare the immunohistochemical expression of prognostic markers p27(Kip1), p45(Skp2) and Ki67 in Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, MCC), small cell neuroendocrine carcinoma of lung and urinary bladder (SNC), and cutaneous squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry was performed using antibodies directed against p27(Kip1), p45(Skp2) and Ki67 on 72 tumour cases: 24 MCC, 25 SCC, and 23 SNC (15 from the lung and eight from the urinary bladder). Percentages of positive cells were determined for each marker and statistically analysed. Expression profiles on MCC and SCC were significantly different for all three markers. MCC and SNC exhibited significant similarities in their p27(Kip1) and p45(Skp2) expression profiles. In contrast, MCC and SNC differed significantly in their Ki67 proliferation indices, which were much higher in SNC. Additionally, MCC cases showed an association between increased proliferation indices and the appearance of local recurrence(s) and/or metastases. CONCLUSION: The immunohistochemical profile of MCC differs from that of SCC, in spite of their common oncogenesis and the supposed metaplastic origin of MCC, and resembles that of SNC, except for Ki67 levels, which were higher in the latter (characterized by greater biological aggressiveness). High levels of Ki67 also appear to be a prognostic factor in MCC.

Analysis of Variance↗

PubMed2004

Epstein-barr virus-positive gastric carcinoma has a distinct protein expression profile in comparison with epstein-barr virus-negative carcinoma.

PURPOSE: EBV has been detected in 2-16% of gastric carcinomas. However, there is little information available about the gene expression profile of EBV-positive gastric carcinomas. EXPERIMENTAL DESIGN: EBV infection was examined using EBV-encoded small RNAs (EBERs) in situ hybridization, and 63 (5.6%) of 1127 consecutive gastric carcinomas were found to be EBV-positive. The expressions of 27 tumor-associated proteins were evaluated immunohistochemically in 63 EBV-positive gastric carcinomas and 287 EBV-negative carcinomas using the tissue array method. In addition, the genotype of EBV was investigated by PCR amplification of LMP1 (latent membrane protein 1), Epstein-Barr nuclear antigen 2 (EBNA2), and EBNA3B genes. RESULTS: EBV-positive gastric carcinomas are characterized by the presence of lymphoid stroma, proximal location, and predominance in males. In comparison with EBV-negative carcinomas, EBV-positive carcinomas showed frequent loss of expression of p16, smad4, FHIT, and KAI-1 (kangai 1; P < 0.05), but retained the expression of APC (adenomatous polyposis coli), DCC (deleted in colorectal cancer), and some DNA repair proteins (P < 0.05). There was negative association between EBV infection and the expression of MUC1, MUC2, MUC5AC, p53, CEA, C-erbB2, and smad7. Using hierarchical cluster analysis, we divided EBV-positive gastric carcinomas into two clusters. Those patients with cluster 1 (42 cases) carcinomas had a better prognosis than those with cluster 2 (12 cases; P = 0.0002) or those with EBV-negative carcinomas (280 cases; P = 0.0251). Fifty-one (92.7%) of 55 EBV-positive carcinomas demonstrated the 30-bp deletion in LMP1 gene, and 53 (96.4%) of 55 cases were type 1 for EBNA2 and EBNA3B genes. CONCLUSION: EBV-positive gastric carcinomas have a distinct protein expression profile as well as distinct clinicopathological features, as compared with EBV-negative carcinomas. The subclassification of EBV-positive carcinomas, by hierarchical cluster analysis, is significantly associated with patient survival.

Base Sequence↗