Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes
| العنوان: | Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes |
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| المؤلفون: | Michel M van den Heuvel, Johan Bussink, Paul N. Span, Monika G. Looijen-Salamon, Johannes H.A.M. Kaanders, Jasper Lok, Tineke W.H. Meijer, Bastiaan B J Tops |
| المصدر: | Thoracic Cancer, Vol 10, Iss 12, Pp 2289-2299 (2019) Thoracic Cancer, 10, 2289-2299 Thoracic Cancer, 10, 12, pp. 2289-2299 Thoracic Cancer |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | non‐small cell lung cancer, 0301 basic medicine, Pulmonary and Respiratory Medicine, Lung Neoplasms, Glutamine, Cell, Fluorescent Antibody Technique, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], medicine.disease_cause, mutational status, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Neoplasm Staging, Messenger RNA, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], biology, business.industry, Glucose transporter, Original Articles, General Medicine, glycolysis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Glucose, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Mutation, biology.protein, Cancer research, Glutamine metabolism, Adenocarcinoma, Original Article, GLUT1, KRAS, business, Glucose Transporter Type 1, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| الوصف: | Contains fulltext : 215799.pdf (Publisher’s version ) (Open Access) BACKGROUND: Both hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism-related markers were examined in stage I - resectable stage IIIA non-small cell lung cancer (NSCLC). Furthermore, expression of metabolism-related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism. METHODS: Mutation analysis was performed for 97 tumors. Glucose and glutamine metabolism-related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81). RESULTS: Glutamine metabolism-related markers were significantly higher in adeno- than squamous cell NSCLCs. Glucose transporter 1 (GLUT1) protein expression was higher in solid compared to lepidic adenocarcinomas (P < 0.01). In adenocarcinomas, mRNA expression of glutamine transporter SLC1A5 correlated with tumor size (r(p) = 0.41, P = 0.005). Furthermore, SLC1A5 protein expression was significantly higher in adenocarcinomas with worse pTNM stage (r(s) = 0.39, P = 0.009). EGFR-mutated tumors showed lower GLUT1 protein (P = 0.017), higher glutaminase 2 (GLS2) protein (P = 0.025) and higher GLS2 mRNA expression (P = 0.004), compared to EGFR wild-type tumors. GLS mRNA expression was higher in KRAS-mutated tumors (P = 0.019). TP53-mutated tumors showed higher GLUT1 expression (P = 0.009). CONCLUSIONS: NSCLC is a heterogeneous disease, with differences in mutational status and metabolism-related marker expression between adeno- and squamous cell NSCLCs, and also within adenocarcinoma subtypes. GLUT1 and SLC1A5 expression correlate with aggressive tumor behavior in adenocarcinomas but not in squamous cell NSCLCs. Therefore, these markers could steer treatment modification for subgroups of adenocarcinoma patients. TP53, EGFR and KRAS mutations are associated with expression of glucose and glutamine metabolism-related markers in NSCLC. |
| وصف الملف: | application/pdf |
| تدمد: | 1759-7714 1759-7706 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::405265537daea13a05ce68564bf55954Test https://doi.org/10.1111/1759-7714.13226Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....405265537daea13a05ce68564bf55954 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17597714 17597706 |
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