PMID- 31641854
OWN - NLM
STAT- MEDLINE
DCOM- 20200129
LR  - 20200129
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Print)
IS  - 0171-5216 (Linking)
VI  - 146
IP  - 1
DP  - 2020 Jan
TI  - Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of 
      brain metastasis in patients with non-small cell lung cancer.
PG  - 273-285
LID - 10.1007/s00432-019-03059-y [doi]
AB  - PURPOSE: The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway 
      plays a vital role in cancer development and progression. This study aimed to 
      investigate the relationship between genotype variants in mTORC1 pathway and the 
      risk of brain metastasis (BM) in patients with non-small cell lung cancer 
      (NSCLC). METHODS: We extracted genomic DNA from blood samples of 501 NSCLC 
      patients and genotyped eight single-nucleotide polymorphisms (SNPs) in three core 
      genes [mammalian target of rapamycin (mTOR), mammalian lethal with sec-13 protein 
      8 (mLST8) and regulatory-associated protein of mTOR (RPTOR)] of the mTORC1 
      pathway. The associations between these SNPs and the risk of BM development were 
      assessed. RESULTS: The AG/GG genotype of mLST8:rs26865 and TC/CC genotype of 
      mLST8:rs3160 were associated with an increased risk of BM [hazard ratios (HR) 
      2.938, 95% confidence interval (CI) 1.664-5.189, p < 0.001 and HR = 2.490, 95% 
      CI = 1.543-4.016, p < 0.001, respectively]. These risk polymorphisms had a 
      cumulative effect on BM risk, with two risk genotypes exhibiting the highest 
      increased risk (p < 0.001). Furthermore, these risk SNPs were associated with the 
      lymph node metastasis (N2/3), body mass index (BMI) (>/= 25 kg/m(2)), high level of 
      squamous cell carcinoma (SCC) antigen and Ki-67 proliferation index. Moreover, 
      patients with AG/GG genotype of mLST8:rs26865 had significantly lower median 
      overall survival than those with AA genotype (12.1 months versus 21.6 months, 
      p = 0.04). CONCLUSIONS: Our results indicate that polymorphisms in mTORC1 pathway 
      were significantly associated with increased risk of BM and may be valuable 
      biomarkers to identify NSCLC patients with a high risk of BM.
FAU - Xu, Yiquan
AU  - Xu Y
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Huang, Yina
AU  - Huang Y
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Weng, Lihong
AU  - Weng L
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Zheng, Jiankun
AU  - Zheng J
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Huang, Yi
AU  - Huang Y
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Lin, Ying
AU  - Lin Y
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Zhao, Yunan
AU  - Zhao Y
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
FAU - Li, Hongru
AU  - Li H
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China. 
      386228200@qq.com.
AD  - Department of Respiratory Medicine and Critical Care Medicine, Fujian Provincial 
      Hospital, No. 134 East Street, Fuzhou, 350001, China. 386228200@qq.com.
FAU - Chen, Yusheng
AU  - Chen Y
AUID- ORCID: 0000-0003-1303-0164
AD  - Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China. 
      cysktz2019@163.com.
AD  - Department of Respiratory Medicine and Critical Care Medicine, Fujian Provincial 
      Hospital, No. 134 East Street, Fuzhou, 350001, China. cysktz2019@163.com.
LA  - eng
GR  - 2018GSP008/High-level hospital grants from Fujian Provincial Hospital/
GR  - 2017XQ2046/Startup Fund for scientific research, Fujian Medical University/
PT  - Journal Article
DEP - 20191022
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain Neoplasms/*genetics/metabolism/*secondary
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathology
MH  - DNA, Neoplasm/blood/genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Lung Neoplasms/*genetics/metabolism/pathology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/*genetics/metabolism
MH  - Middle Aged
MH  - Mutation
MH  - Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - Signal Transduction
PMC - PMC6942024
OTO - NOTNLM
OT  - Biomarker
OT  - Brain metastasis
OT  - Genetic polymorphisms
OT  - Risk
OT  - mTORC1
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/10/24 06:00
MHDA- 2020/01/30 06:00
PMCR- 2019/10/22
CRDT- 2019/10/24 06:00
PHST- 2019/07/28 00:00 [received]
PHST- 2019/10/16 00:00 [accepted]
PHST- 2019/10/24 06:00 [pubmed]
PHST- 2020/01/30 06:00 [medline]
PHST- 2019/10/24 06:00 [entrez]
PHST- 2019/10/22 00:00 [pmc-release]
AID - 10.1007/s00432-019-03059-y [pii]
AID - 3059 [pii]
AID - 10.1007/s00432-019-03059-y [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2020 Jan;146(1):273-285. doi: 
      10.1007/s00432-019-03059-y. Epub 2019 Oct 22.