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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 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.

SUBMITTER: Li SH

PROVIDER: S-EPMC5558018 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma.

Li Shau-Hsuan SH Chien Chih-Yen CY Huang Wan-Ting WT Luo Sheng-Dean SD Su Yan-Ye YY Tien Wan-Yu WY Lan Ya-Chun YC Chen Chang-Han CH

Scientific reports 20170815 1

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-m ...[more]

PMID: 28811537

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Project description:Depth of invasion (DOI) can be calculated preoperatively by MRI, and whether MRI-determined DOI can predict prognosis as well as whether it can be used as an indicator of neck dissection in cT1N0 tongue squamous cell carcinoma (SCC) remains unknown. The main goal of the current study was to answer these unknowns. A total of 151 patients with surgically treated cT1N0 tongue SCC were retrospectively enrolled, and MRI-determined DOI was measured based on T1-weighted layers with a 3.0T scan. The Chi-square test was used to evaluate the association between clinical pathologic variables and neck lymph node metastasis, and the factors that were significant in the Chi-square test were then analyzed in a multivariate logistic regression analysis model to determine the independent predictors. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS), and the Kaplan-Meier method (log-rank test) was used to calculate the LRC and DSS rates. The factors that were significant in univariate analysis were then analyzed in the Cox model to determine the independent prognostic factors. A value of p < 0.05 was considered significant, and all statistical analyses were performed with SPSS 20.0. Occult neck lymph node metastasis was noted in 26 (17.2%) patients, and the ROC curve indicated that the optimal cutoff value of MRI-determined DOI was 7.5 mm for predicting neck lymph node metastasis, with a sensitivity of 86.9%. The factors of lymphovascular invasion, MRI-determined DOI, pathologic DOI, and pathologic tumor grade were significantly associated with the presence of neck lymph node metastasis in univariate analysis, and further logistic regression analysis confirmed the independence of lymphovascular invasion, MRI-determined DOI, and pathologic DOI in predicting neck lymph node metastasis. The 5-year LRC and DSS rates were 84% and 90%, respectively. Cox model analysis suggested the MRI-determined DOI was an independent prognostic factor for both LRC and DSS. Therefore, elective neck dissection is suggested if MRI-determined DOI is greater than 7.5 mm in cT1N0 tongue SCC, and MRI-determined DOI ≥ 7.5 mm indicates additional risk for disease recurrence and cancer-related death.

Dataset Information

Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma.

Publications

Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma.

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