title: VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients.
abstract: Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P<0.05) by multivariate Cox analysis. The further functional assay revealed that VAV3 knockdown regulated CSC activation and ovarian cancer cell proliferation and sensitized paclitaxel (PTX)-resistant cancer cells to PTX treatment. Taken together, we identified by high-throughput analysis of CSCs that VAV3 overexpression is a novel biomarker for poor prognosis and survival in ovarian carcinoma.
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kwon
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.|2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Gwang-Il
authors.initials: GI
authors.lastname: Kim
authors.affiliation: 2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: 2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Song
authors.affiliation: 3 Department of Biomedical Science, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Kyu-Beom
authors.initials: KB
authors.lastname: Kwack
authors.affiliation: 4 Department of Gynecologic Oncology, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Lee
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.|2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Hae-Youn
authors.initials: HY
authors.lastname: Kang
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.|2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Tae-Heon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.|2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Heo
authors.affiliation: 1 Department of Pathology, College of Medicine, CHA University , Sungnam, Republic of Korea.|2 Institute for Clinical Research, College of Medicine, CHA University , Sungnam, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: An
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human