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Published on: September 18, 2020
Relation between outcomes and localisation of p-mTOR expression in gastric cancer
T Murayama1, M Inokuchi, Y Takagi
1Department of Surgical Oncology, Tokyo Medical and Dental University, Yushima, Bunkyo, Japan.
Abstract:
The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2-4, P=0.003), involved lymph nodes (P=0.010), and tumour stage (I vs II-IV, P=0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (P<0.001,=0.035, and <0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P=0.037) and overall survival (OS, P=0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P=0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.
Insights
The location of phosphorylated mammalian target of rapamycin (p-mTOR) in gastric cancer cells impacts patient outcomes. Cytoplasmic p-mTOR correlates with poorer survival, while nuclear p-mTOR is linked to better survival, suggesting its localization is key in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The mammalian target of rapamycin (mTOR) pathway is crucial for cell growth and proliferation.
- mTOR is a potential therapeutic target in various cancers, including gastric cancer.
- Understanding mTOR signaling in gastric cancer is vital for improving patient outcomes.
Purpose of the Study:
- To investigate the correlation between phosphorylated mTOR (p-mTOR) expression and localization with clinicopathological features and survival in gastric cancer patients.
- To examine the relationship between p-mTOR and its upstream regulator, phosphorylated Akt (p-Akt).
Main Methods:
- Immunohistochemical analysis of p-mTOR and p-Akt expression in cytoplasm and nucleus.
- Analysis of tumor samples from 109 gastric adenocarcinoma patients.
- Correlation of protein expression with clinicopathological variables and patient survival (relapse-free and overall survival).
Main Results:
- Cytoplasmic p-mTOR expression positively correlated with tumor invasion depth, lymph node involvement, and tumor stage.
- Nuclear p-mTOR expression negatively correlated with these adverse clinicopathological factors.
- Cytoplasmic p-mTOR was associated with significantly poorer relapse-free survival (RFS) and overall survival (OS), while nuclear p-mTOR was linked to better RFS and OS.
- No significant association was found between p-Akt expression (cytoplasmic or nuclear) and clinicopathological factors or survival.
Conclusions:
- The subcellular localization of p-mTOR, not just its expression level, is a critical determinant of tumor progression and patient outcomes in gastric cancer.
- Targeting or modulating p-mTOR localization may represent a novel therapeutic strategy for gastric cancer.
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