Altered levels of mitochondrial proteins have been proposed as biomarker for thyroid cancer.

we tested the discriminatory power of the combination of the evaluation of the metabolic status as signaled by the gene expression level of PGC-1α, positive regulator of oxidative metabolism and mitochondrial biogenesis, and plasma ND4/ND1 ratios (mitochondrial genes increased in thyroid cancer). We grouped subjects as high and low for PGC-1α gene expression and compared ND4/ND1 ratios between groups.

number of patients with carcinomas in high group was higher than in low group, whereas in hyperplasia group the distribution in the groups was not statistically significantly different, indicating that the evaluation of PGC-1α per se can be functionally significant only in carcinomas. This finding is in line with the possible reduction of PGC-1α activity in plasma of cancer patients, despite the increase in mRNA and protein levels that could lead to mitochondrial dysfunction. We also find that ND4/ND1 ratio was significantly higher in carcinoma than in hyperplasia samples with high PGC-1α levels, but not for those with low PGC-1α levels. Since the alterations in ND4/ND1 ratio have been shown to be mainly derived from changes in the tumor, this result further highlights the link between tumor and systemic metabolism, and the relevance of its evaluation for diagnostic purposes.

Differences in PGC-1α expression levels in plasma between patients with thyroid carcinoma and hyperplasia could related to DNA stability. Combined testing of gene expression data can enhance the discriminatory capacity of the ND4/ND1 evaluation using only crude plasma samples.