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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.

SUBMITTER: King ER

PROVIDER: S-EPMC3095702 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.

King Erin R ER Tung Celestine S CS Tsang Yvonne T M YT Zu Zhifei Z Lok Gabriel T M GT Deavers Michael T MT Malpica Anais A Wolf Judith K JK Lu Karen H KH Birrer Michael J MJ Mok Samuel C SC Gershenson David M DM Wong Kwong-Kwok KK

The American journal of surgical pathology 20110601 6

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 carcino ...[more]

PMID: 21451362

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Project description:Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). 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 RT-PCR, 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) between SBOT, LG and HG tumors. Serous borderline ovarian tumors 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 serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas. Total RNA were extracted from microdissected human ovarian surface epithelia (HOSE, n=6), and microdissected serous borderline ovarian tumors (LMP, n=8), low-grade serous ovarian carcinomas (LGOSC, n=13), and 22 high-grade serous ovarian carcinomas (HGOSC, n=22). Gene Expression profiles were then generated with commercial GeneChip Human Genome U133 Plus 2.0 Array. dChip was used to identify significant differentially expressed genes between LMP/LGOSC and HGOSC

Project description:BackgroundAnterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism.Methodology/principal findingsThrough a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K(d) values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2.Conclusion/significanceIn this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.

Dataset Information

The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.

Publications

The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.

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