title: The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.
abstract: Low-grade (LG) serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors; yet the progression from serous borderline tumors to LG serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the 2 groups. Expression profiles were generated from 6 human ovarian surface epithelia, 8 serous borderline ovarian tumors (SBOTs), 13 LG serous ovarian carcinomas, and 24 high-grade (HG) serous ovarian carcinomas. The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors. This finding was validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues, and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P<0.005) among SBOT, LG, and HG tumors. SBOTs exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P=0.013) and HG (P=0.008) serous ovarian carcinoma groups. The progression of SBOT to LG serous ovarian carcinoma may involve the dedifferentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with LG and HG serous ovarian carcinomas.
authors: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors: Erin R
authors: ER
authors: King
authors: Celestine S
authors: CS
authors: Tung
authors: Yvonne T M
authors: YT
authors: Tsang
authors: Zhifei
authors: Z
authors: Zu
authors: Gabriel T M
authors: GT
authors: Lok
authors: Michael T
authors: MT
authors: Deavers
authors: Anais
authors: A
authors: Malpica
authors: Judith K
authors: JK
authors: Wolf
authors: Karen H
authors: KH
authors: Lu
authors: Michael J
authors: MJ
authors: Birrer
authors: Samuel C
authors: SC
authors: Mok
authors: David M
authors: DM
authors: Gershenson
authors: Kwong-Kwok
authors: KK
authors: Wong
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D054337:Cell Dedifferentiation; D002470:Cell Survival; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D013781:Texas / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: C472588:AGR3 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D009363:Neoplasm Proteins