Detection of volatile sulfur compounds (VSCs) in exhaled breath as a potential diagnostic method for oral squamous cell carcinoma

Kwon, Ik Jae; Jung, Tae-Young; Son, Youjeong; Kim, Bongju; Kim, Soung Min; Lee, Jong-Ho

doi:10.1186/s12903-022-02301-3

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…However, both enzymes are able to methylate hydrogen sulfide, which has been demonstrated to have multiple functions in the cell [27] and may be dysregulated in cancer. Elevated levels of methanethiol have been found in patients diagnosed with oral squamous cell carcinoma [28]. In this study, we demonstrate that these enzymes share high sequence and structure conservation, and that the thiol methyltransferase activity of TMT1A is conserved across different species.…”

Section: Discussionsupporting

confidence: 58%

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species

González Dalmasy,

Fitzsimmons,

Frye

et al. 2023

Preprint

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Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species. We found that TMT1A was conserved across rats, mice, chickens, and zebrafish, displaying 85.7%, 84.8%, 60.7% and 51.0% amino acid sequence identity, respectively, with human TMT1A. Because TMT1B was not found in the chicken or zebrafish, we focused our studies on the TMT1A homologs. HEK-293 cells were transfected to express mouse, rat, chicken, or zebrafish homologs of TMT1A and all conferred resistance to the thiol-based HDACIs NCH-51, KD-5170 and romidepsin compared to empty vector-transfected cells. Additionally, all homologs blunted the downstream effects of HDACi treatment such as increased p21 expression, increased acetylated histone H3, and cell cycle arrest. Increased levels of dimethylated romidepsin were also found in the culture medium of cells transfected to express any of the TMT1A homologs after a 24 h incubation with romidepsin compared to empty-vector transfected cells. Our results indicate that the ability of TMT1A to methylate molecules is conserved across species. Animal models may therefore be useful in elucidating the role of these enzymes in humans.

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Section: Discussionsupporting

confidence: 58%

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species

González Dalmasy,

Fitzsimmons,

Frye

et al. 2023

Preprint

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“…13 C-glucose breath tests have been reported as an alternative method to measure insulin sensitivity to screen pre-diabetic and diabetic individuals, in contrast to the invasive hyperinsulinemic-euglycemic clamp ( Mizrahi et al, 2010 ; Hussain et al, 2014 ). Exhaled breath test analysis may also be a promising approach for cancer detection ( Dharmawardana et al, 2020 ; Meng et al, 2021 ; Kwon et al, 2022 ). To date, several breath tests have been successfully applied in the clinic for the assessment of gastroenterological symptoms and diseases.…”

Section: Discussionmentioning

confidence: 99%

Exogenous detection of 13C-glucose metabolism in tumor and diet-induced obesity models

et al. 2022

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Metabolic rewiring is a hallmark feature prevalent in cancer cells as well as insulin resistance (IR) associated with diet-induced obesity (DIO). For instance, tumor metabolism shifts towards an enhanced glycolytic state even under aerobic conditions. In contrast, DIO triggers lipid-induced IR by impairing insulin signaling and reducing insulin-stimulated glucose uptake. Based on physiological differences in systemic metabolism, we used a breath analysis approach to discriminate between different pathological states using glucose oxidation as a readout. We assessed glucose utilization in lung cancer-induced cachexia and DIO mouse models using a U-13C glucose tracer and stable isotope sensors integrated into an indirect calorimetry system. Our data showed increased 13CO2 expired by tumor-bearing (TB) mice and a reduction in exhaled 13CO2 in the DIO model. Taken together, our findings illustrate high glucose uptake and consumption in TB animals and decreased glucose uptake and oxidation in obese mice with an IR phenotype. Our work has important translational implications for the utility of stable isotopes in breath-based detection of glucose homeostasis in models of lung cancer progression and DIO.

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“…Based on the above, exhaled sulfide level was suggested to be a potential biomarker of asthma and COPD [ 196 ]. Changes in exhaled sulfide levels can also be detected in sepsis, and different intestinal diseases including irritable bowel syndrome, colorectal adenoma, oral squamous cell carcinoma and chronic pancreatitis [ 189 , 197 , 198 , 199 , 200 , 201 ]. Due to the limited number of studies and different methodologies used, and the large contribution of oral bacteria to its exhaled level, further studies are needed to explore its potential role as a biomarker of asthma and COPD or other diseases.…”

Section: Exhaled Gaso-transmittersmentioning

confidence: 99%

Exhaled Biomarkers for Point-of-Care Diagnosis: Recent Advances and New Challenges in Breathomics

et al. 2023

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Cancers, chronic diseases and respiratory infections are major causes of mortality and present diagnostic and therapeutic challenges for health care. There is an unmet medical need for non-invasive, easy-to-use biomarkers for the early diagnosis, phenotyping, predicting and monitoring of the therapeutic responses of these disorders. Exhaled breath sampling is an attractive choice that has gained attention in recent years. Exhaled nitric oxide measurement used as a predictive biomarker of the response to anti-eosinophil therapy in severe asthma has paved the way for other exhaled breath biomarkers. Advances in laser and nanosensor technologies and spectrometry together with widespread use of algorithms and artificial intelligence have facilitated research on volatile organic compounds and artificial olfaction systems to develop new exhaled biomarkers. We aim to provide an overview of the recent advances in and challenges of exhaled biomarker measurements with an emphasis on the applicability of their measurement as a non-invasive, point-of-care diagnostic and monitoring tool.

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Detection of volatile sulfur compounds (VSCs) in exhaled breath as a potential diagnostic method for oral squamous cell carcinoma

Cited by 15 publications

References 28 publications

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species

Exogenous detection of 13C-glucose metabolism in tumor and diet-induced obesity models

Exhaled Biomarkers for Point-of-Care Diagnosis: Recent Advances and New Challenges in Breathomics

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