Osteopontin as a potential diagnostic biomarker for ovarian cancer

Jae Hoon Kim, Steven J. Skates, Toshimitsu Uede, Kwong Kwok Wong, John O. Schorge, Colleen M. Feltmate, Ross S. Berkowitz, Daniel W. Cramer, Samuel C. Mok

Research output: Contribution to journalArticlepeer-review

412 Scopus citations

Abstract

Context: Development of new biomarkers for ovarian cancer is needed for early detection and disease monitoring. Analyses involving complementary DNA (cDNA) microarray data can be used to identify up-regulated genes in cancer cells, whose products may then be further validated as potential biomarkers. Objective: To describe validation studies of an up-regulated gene known as osteopontin, previously identified using a cDNA microarray system. Design, Setting, and Participants: Experimental and cross-sectional studies were conducted involving ovarian cancer and healthy human ovarian surface epithelial cell lines and cultures, archival paraffin-embedded ovarian tissue collected between June 1992 and June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated for a pelvic mass between June 1992 and June 2001 in gynecologic oncology services at 2 US academic institutions. Plasma samples from 107 women selected from an epidemiologic study of ovarian cancer initiated between May 1992 and March 1997 were used as healthy controls. Main Outcome Measures: Relative messenger RNA expression in cancer cells and fresh ovarian tissue, measured by real-time polymerase chain reaction as 2-ΔΔCT (a quantitative value representing the amount of osteopontin expression); osteopontin production, localized and scored in ovarian healthy and tumor tissue with immunohistochemical studies; and amount of osteopontin in patient vs control plasma, measured using an enzyme-linked immunoassay. Results: The geometric mean for 2-ΔΔCT for osteopontin expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared with 270.4 in 14 ovarian cancer cell lines (P=.03). The geometric mean 2-ΔΔCT for osteopontin expression in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with 164.0 in 27 microdissected ovarian tumor tissue samples (P=.06). Immunolocalization of osteopontin showed that tissue samples from 61 patients with invasive ovarian cancer and 29 patients with borderline ovarian tumors expressed higher levels of osteopontin than tissue samples from 6 patients with benign tumors and samples of healthy ovarian epithelium from 3 patients (P=.03). Osteopontin levels in plasma were significantly higher (P<.001) in 51 patients with epithelial ovarian cancer (486.5 ng/mL) compared with those of 107 healthy controls (147.1 ng/mL), 46 patients with benign ovarian disease (254.4 ng/mL), and 47 patients with other gynecologic cancers (260.9 ng/mL). Conclusions: Our findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile.

Original languageEnglish (US)
Pages (from-to)1671-1679
Number of pages9
JournalJAMA
Volume287
Issue number13
DOIs
StatePublished - Apr 3 2002

ASJC Scopus subject areas

  • General Medicine

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