PMID- 28811537
OWN - NLM
STAT- MEDLINE
DCOM- 20190315
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Aug 15
TI  - Prognostic significance and function of mammalian target of rapamycin in tongue 
      squamous cell carcinoma.
PG  - 8178
LID - 10.1038/s41598-017-08345-8 [doi]
LID - 8178
AB  - 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.
FAU - Li, Shau-Hsuan
AU  - Li SH
AD  - Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and 
      Chang Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Chien, Chih-Yen
AU  - Chien CY
AD  - Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang 
      Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Huang, Wan-Ting
AU  - Huang WT
AD  - Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung, Taiwan.
FAU - Luo, Sheng-Dean
AU  - Luo SD
AUID- ORCID: 0000-0003-4095-5541
AD  - Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang 
      Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Su, Yan-Ye
AU  - Su YY
AD  - Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang 
      Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Tien, Wan-Yu
AU  - Tien WY
AD  - Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and 
      Chang Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Lan, Ya-Chun
AU  - Lan YC
AD  - Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and 
      Chang Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Chen, Chang-Han
AU  - Chen CH
AD  - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan. chench7@gmail.com.
AD  - Department of Applied Chemistry, and Graduate Institute of Biomedicine and 
      Biomedical Technology, National Chi Nan University, Chi Nan, Taiwan. 
      chench7@gmail.com.
AD  - Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, 
      Kaohsiung, Taiwan. chench7@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170815
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - *Biomarkers, Tumor
MH  - Carcinoma, Squamous Cell/*metabolism/*mortality/pathology/therapy
MH  - Combined Modality Therapy
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Prognosis
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Tongue Neoplasms/*metabolism/*mortality/pathology/therapy
MH  - Treatment Outcome
PMC - PMC5558018
COIS- The authors declare that they have no competing interests.
EDAT- 2017/08/16 06:00
MHDA- 2019/03/16 06:00
PMCR- 2017/08/15
CRDT- 2017/08/17 06:00
PHST- 2017/03/23 00:00 [received]
PHST- 2017/07/06 00:00 [accepted]
PHST- 2017/08/17 06:00 [entrez]
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2019/03/16 06:00 [medline]
PHST- 2017/08/15 00:00 [pmc-release]
AID - 10.1038/s41598-017-08345-8 [pii]
AID - 8345 [pii]
AID - 10.1038/s41598-017-08345-8 [doi]
PST - epublish
SO  - Sci Rep. 2017 Aug 15;7(1):8178. doi: 10.1038/s41598-017-08345-8.