Persistence of stem cell metabolism in cancers as a failure of differentiation

Tumor glucose uptake was measured by FDG-PET in 859 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake values (SUV) distributions and tested for association between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we performed pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal with a low peak at SUV 2-4 and a high peak at SUV 8-11. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and of death. Carbohydrate metabolism and the pentose related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/ high SUV clusters. Comparison of gene expression pattern in cancer with high and low SUV.