Figure 3 from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

• DOI: 10.1158/2159-8290.28713617
• Publication Date: 2025-04-02T07:23:09Z
• Authors: Ling Cai; Nia G. Hammond; Alpaslan Tasdogan; Massar Alsamraae; Chendong Yang; Robert B. Cameron; Peiran Quan; Ashley Solmonson; Wen Gu; Panayotis Pachnis; Mayher Kaur; Brianna K. Chang; Qin Zhou; Christopher T. He...; Quyen N. Do; Luiza Martins Nas...; Jessalyn M. Ubell...; Akash Kaushik; Maia G. Clare; Isabel N. Alcazar; Katarzyna Kurylowicz; Joseph D. Marcucc...; Gabriele Allies; Andrea Kutritz; Joachim Klode; Vijayashree Ramesh; Thomas J. Rogers; Aparna D. Rao; Hannah E. Crentsil; Hong Li; Fang Brister; Phyllis McDaniel; Xiaohong Xu; Bret M. Evers; Lauren G. Zacharias; Jessica Sudderth; Jian Xu; Thomas P. Mathews; Dwight Oliver; John D. Minna; John Waters; Sean J. Morrison; Kemp H. Kernstine; Brandon Faubert; Ralph J. DeBerard...

<p>Increased ¹³C enrichment in the TCA cycle predicts reduced survival. <b>A,</b>¹³C enrichment in the adjacent lung and tumors with high or low TCA cycle labeling. Fractional enrichments of glycolytic (M+3) and TCA cycle (M+2) metabolites are normalized to enrichment of glucose (M+6) within the tissue. <b>B</b> and <b>C,</b> Overall (<b>B</b>) and recurrence-free (<b>C</b>) survival in patients whose tumors have high or low TCA cycle labeling. The groups include tumors above or below the median for total ¹³C enrichment in citrate, glutamate, and malate. <b>D</b> and <b>E,</b> Overall (<b>D</b>) and recurrence-free (<b>E</b>) survival in patients whose tumors have high or low M+2 enrichment. <b>F,</b>¹³C labeling and clinical factors and relationship to overall survival. <b>G</b> and <b>H,</b> TCA cycle labeling fractions in the adjacent lung (calculated and grouped as in <b>B</b> and <b>C</b>) do not correlate with overall (<b>G</b>) or recurrence-free (<b>H</b>) survival. <b>I,</b> Spearman correlation analysis of labeling features (M+2 and labeled fraction) with clinical metrics. Differences in ¹³C enrichment (<b>A</b>) were determined using a Kruskal–Wallis test with Dunn’s test. Survival differences were assessed by the log-rank (Mantel–Cox) test. BMI, body mass index; MIB-1, Mindbomb Homolog-1; SUV_max, maximum FDG-PET standardized uptake value; TLG 40%, total lesion glycolysis, 40% threshold; AUC120, total area under the curve at 120 seconds, calculated from dynamic contrast-enhanced MRI; N positive, lymph node positive. *,P<0.05; **,P<0.01; ****, P<0.0001. (High TCA vs Adj. Lung), #, P<0.05; ##, P<0.01.; ###, P<0.001) (Low TCA vs. Adj. Lung)</p>