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Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma
Anterior gradient 2 protein belongs to a family of chaperone‐like proteins, namely protein disulfide isomerase. Generally, AGR2 is highly expressed in mucus‐secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR2 and cell cycle molecules in epithelial ovarian cancer and it...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051166/ https://www.ncbi.nlm.nih.gov/pubmed/29845750 http://dx.doi.org/10.1002/cam4.1530 |
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author | Alves, Mariana Rezende e Melo, Natalia Cruz Barros‐Filho, Mateus Camargo do Amaral, Nayra Soares Silva, Felipe Ilelis de Barros Baiocchi Neto, Glauco Soares, Fernando Augusto de Brot Andrade, Louise Rocha, Rafael Malagoli |
author_facet | Alves, Mariana Rezende e Melo, Natalia Cruz Barros‐Filho, Mateus Camargo do Amaral, Nayra Soares Silva, Felipe Ilelis de Barros Baiocchi Neto, Glauco Soares, Fernando Augusto de Brot Andrade, Louise Rocha, Rafael Malagoli |
author_sort | Alves, Mariana Rezende |
collection | PubMed |
description | Anterior gradient 2 protein belongs to a family of chaperone‐like proteins, namely protein disulfide isomerase. Generally, AGR2 is highly expressed in mucus‐secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR2 and cell cycle molecules in epithelial ovarian cancer and its implications on prognosis. One hundred seventy‐five patient's samples that were diagnosed with primary epithelial ovarian carcinoma were selected. All the patients were treated with platinum‐taxane standard chemotherapy after surgery and CA125 serum levels were routinely determined. Four‐micrometer‐thick sections were processed by immunohistochemistry using an automated immunostainer, Ventana BenchMark AutoStainer with AGR2, cyclin D1, p21WAF1, and p53. Forty‐nine of 167 cases (29.3%) showed strong to moderate cytoplasmic marking of AGR2, and 118 (70.7%) had weak to negative expression. The absence of the AGR2 protein was observed in high‐grade serous carcinoma (P < .001) and significantly associated with disease‐free survival (DFS; P = .034). The expression of G1‐S phase‐regulatory proteins showed loss of p21 in high‐grade serous carcinoma (P < .001) and was related with poor DFS (P = .003). Strong and diffuse immunoexpression of p53 plus complete absence of p53 staining was interpreted as likely indicating a TP53 gene mutation. This result showed worse DFS alone (P = .012) and combined with low levels of AGR2 (P = .005). The expression profile of AGR2 and cell cycle proteins here presented was showed as good prognosis marker in epithelial ovarian cancer. This finding suggests AGR2 and as putative biomarker of disease progression in chemotherapy‐treated high‐grade serous carcinoma patients. |
format | Online Article Text |
id | pubmed-6051166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60511662018-07-20 Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma Alves, Mariana Rezende e Melo, Natalia Cruz Barros‐Filho, Mateus Camargo do Amaral, Nayra Soares Silva, Felipe Ilelis de Barros Baiocchi Neto, Glauco Soares, Fernando Augusto de Brot Andrade, Louise Rocha, Rafael Malagoli Cancer Med Cancer Biology Anterior gradient 2 protein belongs to a family of chaperone‐like proteins, namely protein disulfide isomerase. Generally, AGR2 is highly expressed in mucus‐secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR2 and cell cycle molecules in epithelial ovarian cancer and its implications on prognosis. One hundred seventy‐five patient's samples that were diagnosed with primary epithelial ovarian carcinoma were selected. All the patients were treated with platinum‐taxane standard chemotherapy after surgery and CA125 serum levels were routinely determined. Four‐micrometer‐thick sections were processed by immunohistochemistry using an automated immunostainer, Ventana BenchMark AutoStainer with AGR2, cyclin D1, p21WAF1, and p53. Forty‐nine of 167 cases (29.3%) showed strong to moderate cytoplasmic marking of AGR2, and 118 (70.7%) had weak to negative expression. The absence of the AGR2 protein was observed in high‐grade serous carcinoma (P < .001) and significantly associated with disease‐free survival (DFS; P = .034). The expression of G1‐S phase‐regulatory proteins showed loss of p21 in high‐grade serous carcinoma (P < .001) and was related with poor DFS (P = .003). Strong and diffuse immunoexpression of p53 plus complete absence of p53 staining was interpreted as likely indicating a TP53 gene mutation. This result showed worse DFS alone (P = .012) and combined with low levels of AGR2 (P = .005). The expression profile of AGR2 and cell cycle proteins here presented was showed as good prognosis marker in epithelial ovarian cancer. This finding suggests AGR2 and as putative biomarker of disease progression in chemotherapy‐treated high‐grade serous carcinoma patients. John Wiley and Sons Inc. 2018-05-29 /pmc/articles/PMC6051166/ /pubmed/29845750 http://dx.doi.org/10.1002/cam4.1530 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Alves, Mariana Rezende e Melo, Natalia Cruz Barros‐Filho, Mateus Camargo do Amaral, Nayra Soares Silva, Felipe Ilelis de Barros Baiocchi Neto, Glauco Soares, Fernando Augusto de Brot Andrade, Louise Rocha, Rafael Malagoli Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title | Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title_full | Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title_fullStr | Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title_full_unstemmed | Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title_short | Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
title_sort | downregulation of agr2, p21, and cyclin d and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051166/ https://www.ncbi.nlm.nih.gov/pubmed/29845750 http://dx.doi.org/10.1002/cam4.1530 |
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