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In silico evaluation of DNA Damage Inducible Transcript 4 gene (DDIT4) as prognostic biomarker in several
Joseph A Pinto1, Christian Rolfo2, Luis E Raez3
1Unidad de Investigación Básica y Traslacional, Oncosalud-AUNA, Av. Guardia Civil 571, San Borja. Lima 41, Peru.
Abstract:
DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress. High levels of DDIT4 were significantly associated with a worse prognosis in acute myeloid leukemia, breast cancer, glioblastoma multiforme, colon, skin and lung cancer. Conversely, a high DDIT4 expression was associated with an improved prognostic in gastric cancer. DDIT4 was not associated with the outcome of ovarian cancers. Analysis with data from the Cell Miner Tool in 60 cancer cell lines indicated that although rapamycin activity was correlated with levels of MTOR, it is not influenced by DDIT4 expression. In summary, DDIT4 might serve as a novel prognostic biomarker in several malignancies. DDIT4 activity could be responsible for resistance to mTOR inhibitors and is a potential candidate for the development of targeted therapy.
Insights
The DDIT4 gene, linked to cancer progression, acts as a prognostic biomarker across various cancers. High DDIT4 expression indicates a worse outcome in most cancers but an improved one in gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The DDIT4 gene encodes a protein that inhibits mTOR, particularly under stress.
- In vitro studies suggest DDIT4 expression may promote cancer progression.
- Previous research identified DDIT4 as a prognostic factor in triple-negative breast cancer resistant to neoadjuvant chemotherapy.
Purpose of the Study:
- To investigate the association between DDIT4 gene expression and patient outcomes across diverse cancer types.
- To evaluate DDIT4 as a potential prognostic biomarker in multiple malignancies.
- To explore the relationship between DDIT4 expression, mTOR activity, and response to mTOR inhibitors.
Main Methods:
- In silico analysis using online platforms.
- Meta-analysis of pooled datasets from KM Plotter and SurvExpress.
- Analysis of 60 cancer cell lines using the Cell Miner Tool.
Main Results:
- High DDIT4 expression correlated with worse prognosis in acute myeloid leukemia, breast cancer, glioblastoma, colon, skin, and lung cancers.
- Conversely, high DDIT4 expression was linked to improved prognosis in gastric cancer.
- DDIT4 expression did not significantly impact outcomes in ovarian cancer or rapamycin activity in cancer cell lines.
Conclusions:
- DDIT4 may serve as a novel prognostic biomarker in several cancer types.
- DDIT4 activity could contribute to resistance against mTOR inhibitors.
- DDIT4 is a potential target for developing new cancer therapies.
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