Metabolic adaptations are hallmark of cancer and could develop new diagnostic/therapeutic tools. Only about 50% patients who undergo thyroidectomy due to suspicion of thyroid cancer (TC) actually have the disease, highlighting the diagnostic limitations of current tools.

We analyzed blood and thyroid tissue from 2 independent cohorts of patients undergoing thyroidectomy for suspected TC. Histological and immunohistochemically analysis of tissue made. DNA from plasma, PBMCs and tissue analyzed by qPCR. Mitochondrial genes ND1 and ND4 analyzed for their potential as biomarkers.

histological comparisons of TC and hyperplasia revealed higher proliferation, apoptotic rates and enhanced vascular alterations in the former, and increased levels phosphorylated-AKT, suggestive of alterations in mitochondrial distribution. Both are common metabolic adaptations in tumors. These together with reduced mtDNA (mitochondrial DNA) copy number and elevated levels of mitochondrial antioxidant PRX3 in cancer tissue suggest presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of mtDNA, inversely correlated with those in tissue, suggesting that higher cell death rates were linked to lower mtDNA. Correlation of mtDNA levels in tissue and PBMCs further stressed interconnection between systemic and tumor metabolism. Evaluation of ND1 in plasma, PBMCs and tissue, suggested that could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue. In contrast, ND4 would be informative of tumor development, with ND4/mtDNA ratio specifically altered in tumor context.

metabolic dysregulation in TC can be monitored accurately in blood samples and might be exploited for the discrimination of cancer from hyperplasia.