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Expression of key mTOR pathway components in pancreatic ductal adenocarcinoma: A multicenter study for clinicopathologic and prognostic significance
- Source :
- Cancer letters. 395
- Publication Year :
- 2017
-
Abstract
- Thus far, clinicopathologic and prognostic significance of mTOR signaling pathway in pancreatic ductal adenocarcinoma (PDAC) remains unclear, although it is involved in PDAC. In this study, total (t-) and phosphorylated (p-) mTOR, 4EBP1 and P70S6K, were investigated. It was found that most aforementioned proteins were related to malignant and progressive phenotypes, especially histological grade, in independent development and validation cohorts of PDAC. In the development cohort, high expression and/or phosphorylation of mTOR, 4EBP1 and P70S6K were all univariately associated with poor tumor-specific survival, whereas p-mTOR, p-4EBP1 and p-P70S6K, adjusted for clinicopathologic variables, unlike t-mTOR, t-4EBP1 and t-P70S6K, were shown to be independent prognostic factors in multivariate analysis. Interestingly and importantly, the independently significant impacts of p-mTOR and p-4EBP1 on tumor-specific survival were confirmed in the validation cohort. Contrarily, t-mTOR and t-4EBP1 were only univariately significant, while t-P70S6K and p-P70S6K were not prognostic. Finally, mTOR and EIF4EBP1, genes encoding mTOR and 4EBP1, also serve as prognostic indicators in the publicly available TCGA RNA-sequencing database. Our data indicate that expression and activation, especially the latter, of mTOR and 4EBP1, might have clinicopathologic and prognostic significance in PDAC.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Pancreatic ductal adenocarcinoma
Multivariate analysis
Cell Cycle Proteins
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
PI3K/AKT/mTOR pathway
Adaptor Proteins, Signal Transducing
Aged
Aged, 80 and over
Tissue microarray
business.industry
TOR Serine-Threonine Kinases
Ribosomal Protein S6 Kinases, 70-kDa
Middle Aged
Phosphoproteins
Prognosis
Phenotype
Pancreatic Neoplasms
EIF4EBP1
030104 developmental biology
030220 oncology & carcinogenesis
Cohort
Immunohistochemistry
Female
business
Carcinoma, Pancreatic Ductal
Signal Transduction
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 395
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....faee20271cf1032fc5a9a33474041b0b