Warburg effect in malign thyroid tissue evidenced using FTIR spectroscopy.

[BACKGROUND/OBJECTIVES] Thyroid cancer is the most common endocrine malignancy; the clinical approach of nodular thyroid involves ultrasonography (USG) TI-RADS classification, clinical symptoms, and biopsies according to the Bethesda System, highlighting that biomarkers also support diagnosis. The main objective of this research is to compare the chemometric changes by Fourier transform infrared (FTIR) spectroscopy analysis between benign tumor (BT) vs. malignant neoplasm (MN) and thyroid pathology (TP) vs. healthy tissue (HT).

[METHODS] Biopsies of thyroid nodular disease were obtained and analyzed by ATR-FTIR spectroscopy; thereafter, BT and MN biomolecular compounds were compared, as well as TP vs HT. Prior biopsies, laboratory blood tests, USG TI-RADS classification, and thyroid cytopathology report (BETHESDA classifier) were obtained.

[RESULTS] Laboratory blood tests showed that glucose and urea levels were similar in BT and MN, but in MN, the creatinine increased, and the albumin decreased compared to BT, with no differences in thyroid hormones. About the TI-RADS scoring system in the MN group, 52 % were unknown, followed by 4 (30 %). However, no significant differences in the size of the tumors were shown. The most reported Bethesda for BT was I, followed by IV and V. Contrary for the MN was VI, followed by V. The FTIR analysis showed shifts in all the analyzed biomolecules, highlighting the evidence of the Warburg effect on MN. Moreover, an increase in protein vs. lipid and protein vs. DNA (1650/1453 and 1550/1082 ratios) was observed, as well as decreased levels of DNA content about proteins and lipids (1550/1082 and 1082/1453 ratios). Besides, structural changes related to lipids (2962 cm-1, 2877 cm-1), fatty acids (1401 cm-1), amide III (1317 cm-1), and nucleic acid (1239 cm-1) were found on TP in comparison to HT. In this sense, TP showed decreased levels in proteins vs DNA and increased levels of DNA compared to lipids CH2.

[CONCLUSIONS] Metabolic alteration in MN was evidenced, reflecting the "Warburg effect," with a significant decrease in lipids and DNA compared to protein content. In the same way, structural changes related to lipids, fatty acids, amide III, and nucleic acids were found in TP compared to HT. However, more studies are needed.