Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma
Background. Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanc...
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doaj-6005c92d2ab64b34aca2cc2ed41377b02020-11-24T22:08:55ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/508587508587Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell CarcinomaSheng-Dean Luo0Yi-Ju Chen1Chien-Ting Liu2Kun-Ming Rau3Yi-Ching Chen4Hsin-Ting Tsai5Chang-Han Chen6Tai-Jan Chiu7Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanDepartment of Anatomic Pathology, E-Da hospital, I-Shou University, Kaohsiung 83301, TaiwanChang Gung University College of Medicine, Kaohsiung 83301, TaiwanChang Gung University College of Medicine, Kaohsiung 83301, TaiwanChang Gung University College of Medicine, Kaohsiung 83301, TaiwanKaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanKaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanChang Gung University College of Medicine, Kaohsiung 83301, TaiwanBackground. Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF). An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.http://dx.doi.org/10.1155/2015/508587 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sheng-Dean Luo Yi-Ju Chen Chien-Ting Liu Kun-Ming Rau Yi-Ching Chen Hsin-Ting Tsai Chang-Han Chen Tai-Jan Chiu |
spellingShingle |
Sheng-Dean Luo Yi-Ju Chen Chien-Ting Liu Kun-Ming Rau Yi-Ching Chen Hsin-Ting Tsai Chang-Han Chen Tai-Jan Chiu Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma BioMed Research International |
author_facet |
Sheng-Dean Luo Yi-Ju Chen Chien-Ting Liu Kun-Ming Rau Yi-Ching Chen Hsin-Ting Tsai Chang-Han Chen Tai-Jan Chiu |
author_sort |
Sheng-Dean Luo |
title |
Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma |
title_short |
Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma |
title_full |
Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma |
title_fullStr |
Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma |
title_full_unstemmed |
Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma |
title_sort |
osteopontin involves cisplatin resistance and poor prognosis in oral squamous cell carcinoma |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
Background. Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF). An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT. |
url |
http://dx.doi.org/10.1155/2015/508587 |
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