Cancerous glucose metabolism in lung cancer—evidence from exhaled breath analysis

Abstract

Cancer cells prefer hyperglycolysis versus oxidative phosphorylation, even in the presence of oxygen. This phenomenon is used through the FDG-PET scans, and may affect the exhaled volatile signature. This study investigates the volatile signature in lung cancer (LC) before and after an oral glucose tolerance test (OGTT) to determine if tumor cells' hyperglycolysis would affect the volatile signature. Blood glucose levels and exhaled breath samples were analyzed before the OGTT, and 90 min after, in both LC patients and controls. The volatile signature was measured by proton transfer reaction mass spectrometry (PTR-MS). Twenty-two LC patients (age 66.6 ± 12.7) with adenocarcinoma (n = 14), squamous (n = 6), small cell carcinoma (n = 2), and twenty-one controls (age 54.4 ± 13.7; 10 non-smokers and 11 smokers) were included. All LC patients showed a hyperglycolytic state in their FDG-PET scans. Both baseline and post OGTT volatile signatures discriminate between the groups. The OGTT has a minimal effect in LC (a decrease in m/z 54 by 39%, p v = 0.0499); whereas in the control group, five masses (m/z 64, 87,88, 142 and 161) changed by -13%, -49%, -40% and -29% and 46% respectively. To conclude, OGTT has a minimal effect on the VOC signature in LC patients, where a hyperglycolytic state already exists. In contrast, in the control group the OGTT has a profound effect in which induced hyperglycolysis significantly changed the VOC pattern. We hypothesized that a ceiling effect in cancerous patients is responsible for this discrepancy.

On-Line Analysis of Exhaled Breath

“…Hence, there is clearly an unmet need for noninvasive screening test to detect asymptomatic patients at an early stage of disease. Five untargeted on-line studies using PTR [197][198][199] and IMS 200,201 reported VOCs for diagnostic purposes in early stage lung cancer. One study reported lowered concentrations of isoprene acetone and methanol in patients with lung cancer.…”

GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling

“…Among these pathways, glucose metabolism is studied intensively because this pathway is widely used by cancer cells to provide building blocks and to acquire therapeutic resistance (11)(12)(13). LC exhibits a feature of hyperactive glucose metabolism as verified by metabolomic studies and clinical PET-CT examinations (8,14). Glucose transporters, including GLUT1 and GLUT3, are found to be upregulated in LC cells to support their increased glucose uptake (15,16).…”

Breath biopsy for early detection and precision medicine in cancer

“…These changes in cellular metabolism favour survival in an oxygen deprived environment and result in altered metabolic intermediates that function as the building blocks for new cells, both enabling the growth of rapidly dividing cancer cells, and also altering the profile of VOCs in breath [ 9 ]. As these processes are fundamental to cancer cell survival, such altered cellular metabolism occurs as one of the earliest stages of tumourigenesis [ 10 – 12 ], hence VOCs are excellent candidate biomarkers for early detection of cancer.…”