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Prognostic implication of TSC1 and mTOR expression in gastric carcinoma
Sun-Ju Byeon1, Nayoung Han, Jiwoon Choi
1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Background:
Gastric adenocarcinoma is the sixth most common and third most lethal cancer in the world. Except for HER2-targeted therapy, targeted agents against specific molecules participating in gastric carcinogenesis, including those in the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway have not been proved to be effective. However, some studies have suggested that dysfunction of TSC1 may augment mTOR inhibitor activity.
Methods:
We studied p-mTOR and TSC1 status by immunohistochemical analysis of gastric carcinoma samples using a tissue microarray method and expression values adopted from The Cancer Genome Atlas.
Results:
High p-mTOR and low TSC1 expression status is associated with adverse clinicopathologic parameters. Patients with high p-mTOR levels showed poor survival. Patients with low TSC1 levels showed unfavorable survival status in the overall patients group. The combination of p-mTOR status and TSC1 status provided more strong survival information than using each parameter alone.
Conclusions:
In gastric cancer, high p-mTOR expression level is a statistically significant parameter in multivariate and Kaplan-Meier analyses (log-rank test). In addition to p-mTOR, TSC1 expression provided additional information to predict survival. We therefore suggest that evaluation of both p-mTOR and TSC1 status may be helpful in clinical trials related to mTOR inhibitors.
Insights
High p-mTOR and low TSC1 expression predict poor survival in gastric cancer patients. Evaluating both markers offers valuable prognostic information for mTOR inhibitor clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gastric adenocarcinoma is a leading cause of cancer mortality worldwide.
- Targeted therapies beyond HER2 have shown limited efficacy in gastric cancer.
- The mechanistic target of rapamycin (mTOR) pathway is implicated in gastric carcinogenesis, with potential for mTOR inhibitor activity.
Purpose of the Study:
- To investigate the prognostic significance of p-mTOR and TSC1 expression in gastric cancer.
- To determine if combined evaluation of p-mTOR and TSC1 improves survival prediction.
- To assess the potential utility of these markers in clinical trials involving mTOR inhibitors.
Main Methods:
- Immunohistochemical analysis of p-mTOR and TSC1 expression in gastric carcinoma tissue microarrays.
- Utilized The Cancer Genome Atlas (TCGA) expression data for validation.
- Correlated marker status with clinicopathologic parameters and patient survival.
Main Results:
- High p-mTOR expression correlated with adverse clinicopathologic features and poor patient survival.
- Low TSC1 expression was associated with unfavorable survival outcomes.
- Combined assessment of p-mTOR and TSC1 status provided more robust survival prediction than individual markers.
Conclusions:
- High p-mTOR expression is a significant independent prognostic factor in gastric cancer.
- TSC1 expression offers additional prognostic value beyond p-mTOR.
- Evaluating both p-mTOR and TSC1 status may aid in patient stratification for mTOR inhibitor-based clinical trials.
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