Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma
Abstract Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and surv...
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doaj-fd2698bc2bc24049b38305677a64d1592020-12-08T01:51:22ZengNature Publishing GroupScientific Reports2045-23222017-08-017111010.1038/s41598-017-08345-8Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinomaShau-Hsuan Li0Chih-Yen Chien1Wan-Ting Huang2Sheng-Dean Luo3Yan-Ye Su4Wan-Yu Tien5Ya-Chun Lan6Chang-Han Chen7Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial HospitalAbstract Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of cell proliferation by MTT and BrdU assays. In 4-NQO-induced tongue cancer murine model, mTOR inhibitors significantly decreased the incidence of tongue SCC. In conclusion, p-mTOR overexpression was independently associated with poor prognosis of patients with tongue SCC. In vitro and vivo, mTOR inhibition showed the promising activity in tongue SCC. Our results suggest that inhibition of mTOR signaling pathway may be a novel therapeutic target for tongue SCC.https://doi.org/10.1038/s41598-017-08345-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shau-Hsuan Li Chih-Yen Chien Wan-Ting Huang Sheng-Dean Luo Yan-Ye Su Wan-Yu Tien Ya-Chun Lan Chang-Han Chen |
spellingShingle |
Shau-Hsuan Li Chih-Yen Chien Wan-Ting Huang Sheng-Dean Luo Yan-Ye Su Wan-Yu Tien Ya-Chun Lan Chang-Han Chen Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma Scientific Reports |
author_facet |
Shau-Hsuan Li Chih-Yen Chien Wan-Ting Huang Sheng-Dean Luo Yan-Ye Su Wan-Yu Tien Ya-Chun Lan Chang-Han Chen |
author_sort |
Shau-Hsuan Li |
title |
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
title_short |
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
title_full |
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
title_fullStr |
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
title_full_unstemmed |
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
title_sort |
prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
description |
Abstract Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of cell proliferation by MTT and BrdU assays. In 4-NQO-induced tongue cancer murine model, mTOR inhibitors significantly decreased the incidence of tongue SCC. In conclusion, p-mTOR overexpression was independently associated with poor prognosis of patients with tongue SCC. In vitro and vivo, mTOR inhibition showed the promising activity in tongue SCC. Our results suggest that inhibition of mTOR signaling pathway may be a novel therapeutic target for tongue SCC. |
url |
https://doi.org/10.1038/s41598-017-08345-8 |
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