Fig. 2.

Reduced MPC1 levels are associated with disease aggressiveness and shifts in metabolic activity in PDOs. (a) Immunohistochemistry images showing low (left) and high (right) MPC1 protein levels in PDAC TMA (b) Kaplan-Meier survival analysis of patient tumors with high and low MPC1 protein levels. (c) Bar plots illustrating the association of MPC1 levels with histological grade (p < 0.0001), lymphovascular invasion (p = 0.01) and perineural invasion (p = 0.0009). (d) Box plots illustrating H-scores between basal-like and classical subtypes in TMA of resected PDAC tumors. (e) Box plots showing expression of MPC1 (left) and MPC2 (right) protein in biopsies of metastatic PDAC patient tumors (n = 45). (f) Scatter plots illustrating OCR and ECAR changes in basal-like and classical PDOs treated with a MPC1 inhibitor (UK-5099) following glucose injection (left) and oligomycin injection (right) during a Glycolysis Stress Test. Basal-like PDOs had increased baseline glycolysis levels upon inhibition of MPC1. (g) Scatter plots illustrating OCR and ECAR changes in basal-like and classical PDOs treated with a MPC1 inhibitor (UK-5099) during basal respiration (left) and post FCCP injection (right) during a Mito Stress Test. Basal-like PDOs had increased OCR during basal respiration whereas both basal-like and classical PDOs had increased OCR upon inhibition of MPC1. All ECAR and OCR data points are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001