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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Aspartate Aminotransferase, Cytoplasmic, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Databases, Factual, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, ras, Glutamine, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Malate Dehydrogenase, Mice, Mice, Transgenic, Mutation, Missense, NADP, Neoplasm Proteins, Oxidation-Reduction, Point Mutation, Prognosis, RNA Interference, RNA, Messenger, RNA, Neoplasm, RNA, Small Interfering, Radiation Tolerance, Recombinant Fusion Proteins, Tumor Stem Cell Assay, Up-Regulation.
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Is mutant KRAS associated malic enzyme 1 expression a predictive marker for radiation therapy response in non-small cell lung cancer? Context: Advanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in KRAS that may confer radioresistance. We hypothesized that mutant KRAS can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 (ME1), which may contribute to radioresistance. A doxycycline-inducible mouse model of KRAS (G12D) driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles. ME1 expression was found to be mutant KRAS associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant KRAS, but not wild-type KRAS NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated ME1 and GOT1 expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone.
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KRAS driven glutamine metabolism genes, specifically ME1 and GOT1 reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC. Final Decision: yes