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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparative hybridization of cDNA arrays is a powerful tool for the measurement of differences in gene expression between two or more tissues. We optimized this technique and employed it to discover genes with potential for the diagnosis of ovarian cancer. This cancer is rarely identified in time for a good prognosis after diagnosis. An array of 21,500 unknown ovarian cDNAs was hybridized with labeled first-strand cDNA from 10 ovarian tumors and six normal tissues. One hundred and thirty-four clones are overexpressed in at least five of the 10 tumors. These cDNAs were sequenced and compared to public sequence databases. One of these, the gene HE4, was found to be expressed primarily in some ovarian cancers, and is thus a potential marker of ovarian carcinoma.
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PMID:Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. 1057 Sep 65

Difficulties in the detection, diagnosis, and treatment of ovarian cancer result in an overall low survival rate of women with this disease. A better understanding of the pathways involved in ovarian tumorigenesis will likely provide new targets for early and effective intervention. Here, we have used serial analysis of gene expression (SAGE) to generate global gene expression profiles from various ovarian cell lines and tissues, including primary cancers, ovarian surface epithelia cells, and cystadenoma cells. The profiles were used to compare overall patterns of gene expression and to identify differentially expressed genes. We have sequenced a total of 385,000 tags, yielding >56,000 genes expressed in 10 different libraries derived from ovarian tissues. In general, ovarian cancer cell lines showed relatively high levels of similarity to libraries from other cancer cell lines, regardless of the tissue of origin (ovarian or colon), indicating that these lines had lost many of their tissue-specific expression patterns. In contrast, immortalized ovarian surface epithelia and ovarian cystadenoma cells showed much higher similarity to primary ovarian carcinomas than to primary colon carcinomas. Primary tissue specimens therefore appeared to be a better model for gene expression analyses. Using the expression profiles described above and stringent selection criteria, we have identified a number of genes highly differentially expressed between nontransformed ovarian epithelia and ovarian carcinomas. Some of the genes identified are already known to be overexpressed in ovarian cancer, but several represent novel candidates. Many of the genes up-regulated in ovarian cancer represent surface or secreted proteins such as claudin-3 and -4, HE4, mucin-1, epithelial cellular adhesion molecule, and mesothelin. Interestingly, both apolipoprotein E (ApoE) and ApoJ, two proteins involved in lipid homeostasis, are among the genes highly up-regulated in ovarian cancer. Selected serial analysis of gene expression results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in archival material. These experiments provided additional evidence of the relevance of our findings in vivo. The publicly available expression data reported here should stimulate and aid further research in the field of ovarian cancer.
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PMID:Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. 1110 84

The whey acidic protein (WAP) domain is a conserved motif, containing eight cysteines found in a characteristic 4-disulphide core arrangement, that is present in a number of otherwise unrelated proteins. WAP motifs are present in SLPI and elafin, two antiproteinases located on chromosome 20q12-13, in a locus rich in poorly characterized WAP domain proteins. One of these proteins, which contains two WAP domains, is HE4 (also known as WFDC2), originally described as an epididymis specific protein but more recently suggested to be a putative serum tumour marker for ovarian cancer. We have shown that HE4 is expressed in a number of normal human tissues outside of the male reproductive system, including regions of the respiratory tract and nasopharynx, as well as in a subset of lung tumour cell lines. Comparison of multiple HE4 cDNAs and RT-PCR products with genomic sequence allowed the elucidation of the genomic organization. These studies revealed that HE4 can undergo a complex series of alternative splicing events that can potentially yield five distinct WAP domain containing protein isoforms. These results cast doubt on the potential role of HE4 as a serum tumour marker specific for ovarian cancer and open the door to understanding the function of multiple WAP domain containing protein isoforms arising from a single gene.
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PMID:The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. 1196 50

In an ongoing effort to design an efficacious, cost-effective ovarian cancer screening method, the existing tests, CA 125 and transvaginal sonography, are being optimized and combined in a multimodal strategy, and new promising serum markers, such as mesothelin and HE4, are being developed and evaluated. Detection has been found to improve when multiple serum markers are used in a longitudinal logarithm. The parametric empirical Bayes approach improves screening algorithms by capturing the stability of markers over time in a heterogeneous population. It also has relatively simple extensions to multiple markers. The evaluation of markers increasingly accounts for characteristics of a woman that may affect her marker levels and accounts for the cancer's characteristics, histology, and grade. Receiver operating characteristic curves are helpful for evaluation because they relate a marker's sensitivity to the specificity at which it operates. Large, well-designed randomized controlled trials are under way to gauge the performance of existing screening methods.
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PMID:Ovarian cancer screening. 1295 88

Ovarian cancer, the leading cause of death due to gynecological malignancy, is diagnosed in most cases at an advanced stage. Combined with the paucity of symptoms of early-stage disease, the need to develop novel effective markers for the detection of potentially curable, early-stage disease is self-evident. Comprehensive analyses of somatic gene expression patterns in ovarian cancer were reported previously (n=17) and yielded substantial information on somatically altered genes, information that can potentially be useful in developing early detection markers. To further substantiate the role that these genes play in ovarian cancer tumorogenesis, we surveyed these reports and arranged the significantly altered genes from all reported studies by their chromosomal location (in silico chromosomal clustering). Subsequent comparison of this clustering to known genomic somatic alterations at the DNA level from data obtained using comparative genomic hybridization (CGH) was carried out. The major chromosomal regions that displayed overexpressed genes were correlated with the major CGH-detectable DNA amplification areas at 20q (harboring HE4, SLPI, MYBL2, UBE2C, and SDC4) and 1q (harboring MUC1). These genes may provide insights into ovarian cancer pathogenesis and may also prove to be useful as early detection tools.
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PMID:In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer. 1594 68

Despite the poor prognosis of ovarian cancer and the importance of early diagnosis, there are no reliable noninvasive biomarkers for detection in the early stages of disease. Therefore, to identify novel ovarian cancer markers with potential utility in early-stage screening protocols, we have undertaken an unbiased and comprehensive analysis of gene expression in primary ovarian tumors and normal human ovarian surface epithelium (HOSE) using Serial Analysis of Gene Expression (SAGE). Specifically, we have generated SAGE libraries from three serous adenocarcinomas of the ovary and, using novel statistical tools, have compared these to SAGE data derived from two pools of normal HOSE. Significantly, in contrast to previous SAGE-based studies, our normal SAGE libraries are not derived from cultured cell lines. We have also compared our data with publicly available SAGE data obtained from primary tumors and "normal" HOSE-derived cell lines. We have thus identified several known and novel genes whose expressions are elevated in ovarian cancer. These include but are not limited to CLDN3, WFDC2, FOLR1, COL18A1, CCND1, and FLJ12988. Furthermore, we found marked differences in gene expression patterns in primary HOSE tissue compared with cultured HOSE. The use of HOSE tissue as a control for these experiments, along with hierarchical clustering analysis, identified several potentially novel biomarkers of ovarian cancer, including TACC3, CD9, GNAI2, AHCY, CCT3, and HMGA1. In summary, these data identify several genes whose elevated expressions have not been observed previously in ovarian cancer, confirm the validity of several existing markers, and provide a foundation for future studies in the understanding and management of this disease.
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PMID:Comparative gene expression analysis of ovarian carcinoma and normal ovarian epithelium by serial analysis of gene expression. 1603 Jan 7

Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.
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PMID:The human ovarian teratocarcinoma cell line PA-1 demonstrates a single translocation: analysis with fluorescence in situ hybridization, spectral karyotyping, and bacterial artificial chromosome microarray. 1608 Sep 59

A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.
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PMID:New tumor markers: CA125 and beyond. 1634 44

Epithelial ovarian cancer is neither a common nor a rare disease. In the United States, the prevalence of ovarian cancer in postmenopausal women (1 in 2,500) significantly affects strategies for prevention and detection. If chemoprevention for ovarian cancer were provided to all women over the age of 50, side effects would have to be minimal in order to achieve an acceptable ratio of benefit to risk. This ratio might be improved by identifying subsets of individuals at increased risk or by bundling prevention of ovarian cancer with treatment for other more prevalent conditions. Approximately 10% of ovarian cancers are familial and relate to mutations of BRCA1, BRCA2, and mismatch repair genes. More subtle genetic factors are being sought in women with apparently sporadic disease. Use of oral contraceptive agents for as long as 5 years decreases the risk of ovarian cancer in later life by 50%. In one study, fenretinide (4-HPR) delayed development of ovarian cancer in women at increased risk of developing breast and ovarian cancer. Accrual to confirmatory studies has been prohibitively slow and prophylactic oophorectomy is recommended for women at increased genetic risk. Vaccines may have a role for prevention of several different cancers. Breast and ovarian cancers express mucins that could serve as targets for vaccines to prevent both cancers. Early detection of ovarian cancer requires a strategy with high sensitivity (> 75% for stage I disease) and very high specificity (> 99.6%) to achieve a positive predictive value of 10%. Transvaginal sonography (TVS) has achieved these values in some studies, but is limited by the cost of annual screening in a general population. Two-stage strategies that incorporate both serum markers and TVS promise to be more cost-effective. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risks for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the United Kingdom that will critically test the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125. Recent candidates include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s) and soluble EGF receptor. Proteomic approaches have been used to define a distinctive pattern of peaks on mass spectroscopy or to identify a limited number of critical markers that can be assayed by more conventional methods. Several groups are placing known markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.
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PMID:Prevention and early detection of ovarian cancer: mission impossible? 1730 89

The lack of reliable early detection of ovarian cancer and the absence of specific symptoms result in diagnosis of ovarian cancer at advanced stage in the majority of the patients. Through gene expression profiling we can identify important genes that may help understand the evolution from normal ovarian tissue to ovarian cancer. The gene expression profiles of 7 normal ovaries and 26 ovaries with serous epithelial ovarian cancer (SEOC) were examined by cDNA microarrays using supervised and unsupervised analysis, with sequential significance filtering. Real-time RT-PCR was used to measure and compare the expression levels of 5 selected genes: WAP four-disulfide core domain protein HE4 (WAP, up-regulated), secreted phosphoprotein 1 (SPP1, osteopontin; up-regulated), activin A receptor, type I (ACVR1, up-regulated), tumor necrosis factor (TNF superfamily, member 2; TNF, up-regulated) and decorin (DCN, down-regulated) in 4 epithelial scrapings and in 6 bulk-extracted normal ovaries. The gene expression profile of SEOC was not dependent on the stage of the disease at diagnosis. A supervised microarray data analysis identified a subset of 329 genes showing significant differential expression between SEOC samples and bulk normal ovarian tissue and ovarian surface scrapings, including several new genes such as TNFalpha and activin A receptor type I. The real-time RT-PCR for the up-regulated genes did not differ significantly between normal ovarian epithelial scrapings and bulk-extracted ovaries. However, decorin showed a statistically significant difference (P=0.0073) in expression between epithelial scrapings and bulk-extracted ovaries. Previously uncharacterized genes are associated with the malignant phenotype of SEOC. Bulk normal ovarian tissue may serve as control for SEOC tissue in gene expression profiling. Gene expression profiling and sequential statistical analyses of gene subsets can identify new genes and molecular pathways affecting development of SEOC. The genes of interest can be potential targets for future research of SEOC.
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PMID:Microarray expression identification of differentially expressed genes in serous epithelial ovarian cancer compared with bulk normal ovarian tissue and ovarian surface scrapings. 1798 16


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