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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Autores principales: Shau-Hsuan Li, Chih-Yen Chien, Wan-Ting Huang, Sheng-Dean Luo, Yan-Ye Su, Wan-Yu Tien, Ya-Chun Lan, Chang-Han Chen
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/fd2698bc2bc24049b38305677a64d159
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spelling oai:doaj.org-article:fd2698bc2bc24049b38305677a64d1592021-12-02T11:53:10ZPrognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma10.1038/s41598-017-08345-82045-2322https://doaj.org/article/fd2698bc2bc24049b38305677a64d1592017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08345-8https://doaj.org/toc/2045-2322Abstract 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.Shau-Hsuan LiChih-Yen ChienWan-Ting HuangSheng-Dean LuoYan-Ye SuWan-Yu TienYa-Chun LanChang-Han ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
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
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 Portfolio
publishDate 2017
url https://doaj.org/article/fd2698bc2bc24049b38305677a64d159
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