Uncoupling protein 1 (UCP1) is a
proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat production. Using immunohistochemistry, we investigated the expression of UCP1 and UCP3 in a series of 98 patients with
non-small cell lung cancer (NSCLC) treated with surgery. Expression patterns were correlated with histopathological variables, prognosis, and the expression of
enzymes/
proteins related to cell metabolism. Bronchial epithelium did not express UCP1 or UCP3, while alveolar cells strongly expressed UCP1. In
tumors, strong expression of UCP1 and UCP3 was recorded in 43/98 (43.8%) and 27/98 (27.6%) cases, respectively. UCP1 was significantly associated with squamous cell histology (P = 0.05), whilst UCP3 was more frequently overexpressed in
large cell carcinomas (P = 0.08), and was inversely related to
necrosis (P = 0.009). In linear regression analysis, UCP1 was directly related to markers of glycolysis [
hexokinase (HXKII) and
phosphofructokinase (PFK1)] and anaerobic
glucose metabolism [
pyruvate dehydrogenase kinase (PDK1) and
lactate dehydrogenase (LDH5)]. UCP3 was directly linked with a
glucose transporter (GLUT2), monocarboxylate transporter (MCT2), glycolysis markers (PFK1 and
aldolase), and with the phosphorylation of
pyruvate dehydrogenase (pPDH). Kaplan-Meier survival analysis showed that UCP3 was significantly related to poor prognosis in
squamous cell carcinomas (P = 0.04). UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung
tumors and their expression coincides with increased
glucose absorption, intensified glycolysis, and anaerobic
glucose usage. Whether UCPs are targets for therapeutic interventions in
lung cancer is a hypothesis that demands further investigation.