Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development - PubMed (original) (raw)

Fig. 2. Plasma BCAAs are elevated during subclinical disease

a, Graph of odds ratio (95% confidence interval) for future pancreatic cancer diagnosis among cohort cases and matched controls comparing highest versus lowest quintiles of circulating BCAAs stratified by time from blood collection to the case's cancer diagnosis. Odds ratio (95% confidence interval) from conditional logistic regression models conditioned on matching factors and adjusted for age at blood draw (years, continuous), fasting time (<4, 4–8, 8–12, ≥12 hours, missing) and race/ethnicity (White, Black, other, missing). Red horizontal line marks an odds ratio of 1.0. **b.** Graph of total plasma BCAAs in KPC mice over time and in littermate controls. Each control data point is an average for one mouse over the course of the study (Supplementary Fig. 3b) and values for KPC mice living longer than 19 weeks are averaged for the >19 weeks time point. For weeks 15-17, n = 6 KPC and n = 9 control, _t_-test, _P_=0.001. c, H&E staining of pancreatic tissue obtained from KP–/–C mice and littermate controls at 3-4 weeks of age. Tissue are shown from a control mouse with histologically normal pancreas (left); a KP–/–C mouse with areas of PDAC adjacent to areas of normal pancreas (middle); and a KP–/–C mouse with areas of PDAC and pancreatic intraepithelial neoplasia (closed arrow heads) (right); scale bar = 50μM. d, Mean (±SEM) body weights at 3-4 weeks of age for KP–/–C mice and littermate controls (n = 7 KP–/–C, n = 11 control mice). e, Mean (±SEM) total plasma branched chain amino acid levels from KP–/–C mice and littermate controls at 3-4 weeks of age (n = 10 KP–/–C, n = 14 control mice, _t_-test, P=0.002). f, _P_–values for comparison of circulating amino acid levels in KP–/–C mice and littermate controls at 3-4 weeks of age, cys = cystine (n = 10 KP–/–C, n = 14 control mice), The dashed red line indicates _P_–value of 0.05. g, top, glucose tolerance test in KP–/–C mice and littermate controls at the time of weaning (n = 7 KP–/–C, n = 11 control mice) and bottom, insulin tolerance test in KP–/–C mice and littermate controls at four weeks of age (n = 7 KP–/–C, n = 15 control mice). h, Mean (±SEM) fasting plasma insulin levels from KP–/–C mice and littermate controls at four weeks of age (n = 7 KP–/–C, n = 11 control mice).