Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.

Background Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. Methods We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. Results Compared with the non-DM group ( n =847), patients with DM ( n =235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. Conclusion DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

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