High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels.
The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian cancers. The aim of this study was to further delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in serum. Relative IGFBP-2 expression was measured using quantitative real-time polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian cancer compared to controls and patients with benign gynecological conditions (P = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated with elevated serum IGFBP-2 levels compared to both normal controls and patients with benign gynecological disease. Our findings provide further support that the insulin-like growth factor pathway plays a significant role in epithelial ovarian cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker with utility in detection and monitoring of epithelial ovarian cancer.
Lancaster
J M
JM
H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, 33612, USA. lancasjm@moffitt.usf.edu
Sayer
R A
RA
Blanchette
C
C
Calingaert
B
B
Konidari
I
I
Gray
J
J
Schildkraut
J
J
Schomberg
D W
DW
Marks
J R
JR
Berchuck
A
A
D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000235:genetics / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000235:genetics / Q000601:surgery; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000235:genetics / Q000601:surgery; D016889:Endometrial Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000235:genetics / Q000601:surgery; D010048:Ovarian Cysts / Q000097:blood / Q000235:genetics; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D010053:Ovary / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics / Q000601:surgery; D011300:Preoperative Care; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger