Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes

Abstract

BackgroundBoth 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.MethodsMutation analysis was performed for 97 tumors. Glucose and glutamine metabolism‐related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81).ResultsGlutamine 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).ConclusionsNSCLC 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.

MRI Radiomics Signature as a Potential Biomarker for Predicting KRAS Status in Locally Advanced Rectal Cancer Patients

“…Both SUVcov and SUVmax showed an AUC of 0.65 (17). PET-CT is a great instrument for metabolic demonstration, and some studies presented a relationship between glucose metabolism and RAS status (31). In Pierre's research, SUVmax was the most distinct parameter for KRAS status; in patients with KRAS mutations, SUVmax summary, PET-CT is a direct demonstration of tumor metabolism but still cannot uncover the strong relationship between the parameters of SUV and KRAS status based on the current evidence.…”

Habitat Imaging-Based 18F-FDG PET/CT Radiomics for the Preoperative Discrimination of Non-small Cell Lung Cancer and Benign Inflammatory Diseases

“…To achieve this, glucose transporters are overexpressed in cancer cells to ensure glucose transportation for oncogenic transformation and progression. Regarding SCC, the histopathological subtype can be indicated by high expression of glucose transporter 1 (GLUT1) (38,39), e.g., premalignant lesions of bronchial epithelium (40), which can be reflected by a high SUV in PET images. For ADC, the mass can consist of different levels of cell differentiation to demonstrate heterogeneity.…”

Heterogeneity of Glucose Transport in Lung Cancer

“…SqCC is characterized by high expression of GLUT1 in almost all cases [ 214 , 215 , 216 , 217 ], from the premalignant lesions of bronchial epithelium [ 213 ] to metastatic cancer ( Figure 5 A,B). GLUT1 is upregulated in SqCC by p63, the lineage factor of basal bronchial epithelial cells, and Sox2 [ 5 ], and is associated with SqCC vulnerability to glucose restriction by pharmacological inhibition of GLUT1 [ 4 ].…”