Identification of differentially expressed genes in clinically distinct groups of serous ovarian carcinomas using cDNA microarray.
To identify changes in gene expression in serous epithelial ovarian cancers (SEOC), we utilized cDNA microarrays consisting of 2382 genes with cancer related properties to analyze tumors from 20 patients with defined clinical out-comes. The significance analysis of microarrays method was used to determine differentially expressed genes, leading to the identification of 134 up-regulated and 231 down-regulated genes overall. By increasing the stringency of the statistical selection criteria, 41 over-expressed and 51 under-expressed genes were identified. The median duration of follow-up of the 20 patients was 16.8 months with a median progression free survival of 7.0 months. We found 11 genes that were differentially over-expressed in patients with recurrent disease, and 3 genes (homo sapiens mRNA for Ins P3 5-phophatase, lipoma HMGIC fusion partner-like 2 and CD63 melanoma 1 antigen) in patients who were dead of disease. Subsequently, we examined the distribution of the differentially expressed genes in the cDNA library database from adult human tumor and normal tissues using the DigiNorthern method to identify a subset of genes with relatively restricted tissue distribution. Finally, protein expression of 5 selected genes were further examined using immunohistochemistry applied on a tissue microarray prepared from an independent panel of 93 SEOC tissues. The results provided validation for 2 under-expressed genes (E2F transcription factor 5 and CK14) and 3 over-expressed genes (Bcl2-like 1, COX-2, CD63). Our study demonstrates differential gene expression in clinically distinct groups of SEOC using cDNA microarray. These genes may potentially be useful as biomarkers and/or targets for therapeutic intervention.
Collins
Yvonne
Y
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14261, USA.
Tan
Dong Feng
DF
Pejovic
Tanja
T
Mor
Gil
G
Qian
Feng
F
Rutherford
Thomas
T
Varma
Ram
R
McQuaid
Devin
D
Driscoll
Deborah
D
Jiang
Ming
M
Deeb
George
G
Lele
Shashikant
S
Nowak
Norma
N
Odunsi
Kunle
K
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D050700:E2F5 Transcription Factor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D007120:Immunochemistry; D007527:Isoenzymes / Q000032:analysis; D008565:Membrane Proteins; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012704:Serous Membrane / Q000473:pathology; D060149:Tetraspanin 30; D014018:Tissue Distribution / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis; D015854:Up-Regulation; D051020:bcl-X Protein
D015703:Antigens, CD; C494811:BCL2L1 protein, human; C554586:CD63 protein, human; D050700:E2F5 Transcription Factor; C092558:E2F5 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D060149:Tetraspanin 30; D014157:Transcription Factors; D051020:bcl-X Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases