Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

Abstract

Metabolomics based on untargeted flow infusion electrospray ionization high-resolution mass spectrometry (FIE-HRMS) can provide a snap-shot of metabolism in living cells. Lung Squamous Cell Carcinoma (SCC) is one of the predominant subtypes of Non-Small Cell Lung Cancers (NSCLCs), which usually shows a poor prognosis. We analysed lung SCC samples and matched histologically normal lung tissues from eight patients. Metabolites were profiled by FIE-HRMS and assessed using t-test and principal component analysis (PCA). Differentially accumulating metabolites were mapped to pathways using the mummichog algorithm in R, and biologically meaningful patterns were indicated by Metabolite Set Enrichment Analysis (MSEA). We identified metabolic rewiring networks, including the suppression of the oxidative pentose pathway and found that the normal tricarboxylic acid (TCA) cycle were decoupled from increases in glycolysis and glutamine reductive carboxylation. Well-established associated effects on nucleotide, amino acid and thiol metabolism were also seen. Novel aspects in SCC tissue were increased in Vitamin B complex cofactors, serotonin and a reduction of γ-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts.

Integrative Metabolomic and Lipidomic Profiling of Lung Squamous Cell Carcinoma for Characterization of Metabolites and Intact Lipid Species Related to the Metastatic Potential

“…Glycerol is converted to glycerol-3-phosphate and glycerol-3-phosphate is essential for cell proliferation and growth [23]. The increased glycerol-3-phosphate level was reported in the lung SQCC tissue, compared to normal tissue [24]. In our study, increased levels of glycerol-3-phosphate were observed in the lung SQCC lines with highmetastatic potential, compared with those in normal cells.…”

“…Our study revealed that hypoxanthine and inosine concentrations were increased with increasing metastatic potential. In the previous study, higher levels of hypoxanthine and inosine were observed in lung SQCC tissue, compared to normal tissue [24]. Significantly higher levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were suggested as characteristic of lung SQCC tissues versus lung adenocarcinoma and large cell carcinoma [37].…”

Feasibility of 1 H MR spectroscopy in malignant pulmonary lesions at 3 Tesla: phantom study and clinical verification

“…In vivo ndings of the currently presented research include high amplitude choline concentration for metastatic colon adenocarcinoma as well as prominent lactate peak for lung SCC in a patient with widespread distant metastases, who unfortunately expired after 3 months. Tumor marker concentrations have been consistent with tumor histopathology and have been con rmed in other studies (22,(46)(47)(48)(49)(50)(51)(52)(53)(54). Peak appearance was categorized in three different concentrations de ned as 1+, 2 + and 3+, which may help simply de ne the pathological characteristics in future research.…”

Monitoring methylation‑driven genes as prognostic biomarkers in patients with lung squamous cell cancer

“…LUSC, which usually has a poor prognosis, is one of the major subtypes of lung cancer, and is difficult to treat as patients tend to be older and have a higher incidence of comorbidities (17,18). The occurrence of lung cancer is an intricate biological process involving multiple steps and factors, and is closely related to changes in genetic information.…”