Machine learning-aided metallomic profiling in serum and urine of thyroid cancer patients and its environmental implications

The incidence rate of thyroid cancer has been growing worldwide. Thyroid health is closely related with multiple trace metals, and the nutrients are essential in maintaining thyroid function while the contaminants can disturb thyroid morphology and homeostasis. In this study, we conducted metallomic analysis in thyroid cancer patients (n = 40) and control subjects (n = 40) recruited in Shenzhen, China with a high incidence of thyroid cancer. We found significant alterations in serumal and urinary metallomic profiling (including Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, I, Ba, Tl, and Pb) and elemental correlative patterns between thyroid cancer patients and controls. Additionally, we also measured the serum Cu isotopic composition and found a multifaceted disturbance in Cu metabolism in thyroid disease patients. Based on the metallome variations, we built and assessed the thyroid cancer-predictive performance of seven machine learning algorithms. Among them, the Random Forest model performed the best with the accuracy of 1.000, 0.858, and 0.813 on the training, 5-fold cross-validation, and test set, respectively. The high performance of machine learning has demonstrated the great promise of metallomic analysis in the identification of thyroid cancer. Then, the Shapley Additive exPlanations approach was used to further interpret the variable contributions of the model and it showed that serum Pb contributed the most in the identification process. To the best of our knowledge, this is the first study that combines machine learning and metallome data for cancer identification, and it supports the indication of environmental heavy metal-related thyroid cancer etiology.