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Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma
Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarif...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826307/ https://www.ncbi.nlm.nih.gov/pubmed/31578579 http://dx.doi.org/10.3892/or.2019.7352 |
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author | Shimbo, Akiko Kajiyama, Hiroaki Tamauchi, Satoshi Yoshikawa, Nobuhisa Ikeda, Yoshiki Nishino, Kimihiro Suzuki, Shiro Niimi, Kaoru Sakata, Jun Kikkawa, Fumitaka |
author_facet | Shimbo, Akiko Kajiyama, Hiroaki Tamauchi, Satoshi Yoshikawa, Nobuhisa Ikeda, Yoshiki Nishino, Kimihiro Suzuki, Shiro Niimi, Kaoru Sakata, Jun Kikkawa, Fumitaka |
author_sort | Shimbo, Akiko |
collection | PubMed |
description | Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023–3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077–4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF-β-dependent migration-promoting effect on these CTGF-depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration-promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC. |
format | Online Article Text |
id | pubmed-6826307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-68263072019-11-05 Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma Shimbo, Akiko Kajiyama, Hiroaki Tamauchi, Satoshi Yoshikawa, Nobuhisa Ikeda, Yoshiki Nishino, Kimihiro Suzuki, Shiro Niimi, Kaoru Sakata, Jun Kikkawa, Fumitaka Oncol Rep Articles Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023–3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077–4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF-β-dependent migration-promoting effect on these CTGF-depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration-promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC. D.A. Spandidos 2019-12 2019-10-03 /pmc/articles/PMC6826307/ /pubmed/31578579 http://dx.doi.org/10.3892/or.2019.7352 Text en Copyright: © Shimbo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Shimbo, Akiko Kajiyama, Hiroaki Tamauchi, Satoshi Yoshikawa, Nobuhisa Ikeda, Yoshiki Nishino, Kimihiro Suzuki, Shiro Niimi, Kaoru Sakata, Jun Kikkawa, Fumitaka Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title | Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title_full | Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title_fullStr | Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title_full_unstemmed | Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title_short | Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
title_sort | expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826307/ https://www.ncbi.nlm.nih.gov/pubmed/31578579 http://dx.doi.org/10.3892/or.2019.7352 |
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