title: Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.
abstract: Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurosaki
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Research and Development, EIDIA Co. Ltd, Inashiki, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hanaoka
authors.affiliation: Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyara
authors.affiliation: Department of Translation Medicine and Diagnostics, Morphotek, Inc, Exton, PA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: O'Shannessy
authors.affiliation: Department of Translation Medicine and Diagnostics, Morphotek, Inc, Exton, PA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Somers
authors.affiliation: Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Research and Development, EIDIA Co. Ltd, Inashiki, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sekino
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058975:Folate Receptor 1 / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D058975:Folate Receptor 1
keywords: FRA; diagnostic; folate receptor alpha; ovarian cancer; serum biomarker