In silico evaluation of DNA Damage Inducible Transcript 4 gene (DDIT4) as prognostic biomarker in several malignancies
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Fecha
2017Autor(es)
Bravo, Leny
Fajardo, Williams
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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.
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