Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray

Wang, Kai; Gan, Lu; Jeffery, Eric; Gayle, Margit; Gown, Allen M.; Skelly, Marilyn; Nelson, Peter S.; Ng, WeiLap V.; Schummer, Michèl; Hood, Leroy; Mulligan, John T.

doi:10.1016/s0378-1119(99)00035-9

Cited by 271 publications

(135 citation statements)

References 18 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…A number of groups have previously investigated gene-expression profiling of ovarian cancer using microarrays (Wang et al, 1999;Ismail et al, 2000;Ono et al, 2000;Mok et al, 2001;Shridhar et al, 2001;Welsh et al, 2001). These studies have focused on either the identification of gene products which can serve as ovarian cancerspecific markers (Mok et al, 2001), or on the initiation and progression of ovarian cancer (Ismail et al, 2000;Shridhar et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Predicting biomarkers for ovarian cancer using gene-expression microarrays

et al. 2004

View full text Add to dashboard Cite

Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Here, we used oligonucleotide microarrays complementary to B12 000 genes to establish a gene-expression microarray (GEM) profile for normal ovarian tissue, as compared to stage III ovarian serous adenocarcinoma and omental metastases from the same individuals. We found that the GEM profiles of the primary and secondary tumours from the same individuals were essentially alike, reflecting the fact that these tumours had already metastasised and acquired the metastatic phenotype. We have identified a novel biomarker, mammaglobin-2 (MGB2), which is highly expressed specific to ovarian cancer. MGB2, in combination with other putative markers identified here, could have the potential for screening. Ovarian cancer is the leading cause of death from gynaecological malignancy, with an estimated 24 000 and 6800 new cases in the US and UK, respectively, during (Greenlee et al, 2001Swerdlow et al, 2001). Early-stage disease is largely asymptomatic, and most patients are diagnosed when disease has spread beyond the pelvis with an associated 5-year survival of less than 20% (Ozols, 2002). This is partly due to the lack of reliable screening strategies. While around 90% of women with advanced disease have elevated serum CA125, this marker alone is neither sufficiently sensitive nor specific for use as a screening tool (Menon and Jacobs, 2001). Despite new cytotoxic regimens, survival has remained largely unchanged over the past 20 years. Identification of new molecular signatures of early disease is a key goal of ovarian cancer research.Gene-expression microarray (GEM) profiles have previously been used to compare the expression profile of ovarian cancer with that of the normal ovary (Ono et al, 2000;Welsh et al, 2001). We extended this approach by using a more extensive set of probes (Affymetrix U95Av2), and also characterised metastatic disease in a search for molecular markers of progression. We investigated the potential specificity of a number of putative biomarkers by examining their expression in a panel of other epithelial tissues and tumours. MATERIALS AND METHODS Ovarian tissue samplesFour snap-frozen normal ovarian samples, and six pairs of primary and omental serous adenocarcinoma (Stage IIIC) from the same individuals were collected at the time of surgery at the University College Hospitals NHS Trust. The six paired samples of primary and secondary ovarian cancer were taken at the time of primary surgery prior to chemotherapeutic intervention. The normal ovarian samples were taken at the time of surgery for benign disease. H&E-stained sections were examined and verified histopathologically to be stage III serous adenocarcinomas. All samples comprised at least 70% tumour, except one omental sample which had 5% tumour content. The normal ovarian samples were verified to be free of any pathology, including benign cysts. Ovarian epithelium was macrodissected from the underlying stroma...

show abstract

Section: Discussionmentioning

confidence: 99%

Predicting biomarkers for ovarian cancer using gene-expression microarrays

et al. 2004

View full text Add to dashboard Cite

show abstract

“…A total of 17 genes were identified with reduced expression and another 10 genes with higher expression in the ovarian cancer cell lines compared to the HOSE cell line. Wang et al (1999) and also used cDNA microarrays to monitor gene expression changes in ovarian tumours compared to normal ovaries. There were no common genes between those identified in our study and those in the top 15 overexpressed or under-expressed known genes reported by Wang et al (1999) or the 43 known genes found to be over-expressed by Schummer et al (1999).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

et al. 2001

View full text Add to dashboard Cite

SummaryThe molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted for mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36.

show abstract

“…The prototype of HE4 protein contains two four-disulfide core domains (WFDC2) that often carry antiproteinase activity. Mature HE4 protein is a 20-25 kDa glycoprotein found in the cytoplasm and on membranes of cells and in circulation [8,9].…”

Section: He4 Gene and Its Expressionmentioning

confidence: 99%

“…Structural analysis predicted HE4 to be a protease inhibitor possibly involved in sperm maturation [6]. Using high-density cDNA microarray, Schummer et al and Wang et al independently identified HE4 to be one of the genes overexpressed in ovarian cancer tissues compared to normal ovarian tissues [7,8]. Bingle et al reported that HE4 is expressed in some normal tissues, and HE4 gene undergoes complex splicing, generating multiple proteins [9].…”

Section: Introductionmentioning

confidence: 99%

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Duan

et al. 2016

Expert Review of Molecular Diagnostics

View full text Add to dashboard Cite

Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray

Cited by 271 publications

References 18 publications

Predicting biomarkers for ovarian cancer using gene-expression microarrays

Predicting biomarkers for ovarian cancer using gene-expression microarrays

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Contact Info

Product

Resources

About