A Prospective Study of Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3

Papillary and follicular thyroid cancers are low-grade endocrine malignancy, and most patients usually received thyroidectomy with ablative radioactive iodine therapy. These patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Serum thyroglobulin is the pivotal biomarker in survey of possible residual tumor or recurrence of thyroid cancer. Generally, such patients appear to have the higher residual risk of isolated thyroglobulinemia, and postoperative serum thyroglobulin may suggest distant metastases. Low-risk patients with a non-stimulated postoperative serum thyroglobulin was usually defined of less than 0.4 ng/mL or with thyroid hormone withdrawal thyroglobulin of less than 1.0 ng/mL. However, expensive recombinant human TSH (rhTSH) is usually needed to stimulate serum thyroglobulin for detecting local recurrence or distant metastasis. The issue of earlier biological markers for predicting prognosis of thyroid cancer should be raised.

Exosomes are nanovesicles secreted into extracellular environments. Cancer cell-derived exosomes could be found in plasma, saliva, urine and other body fluid of patients with cancer. A growing evidence suggests that exosomes could be used as biomarkers to be the diagnosis and prognosis of malignant tumors. Exosomes are 40-100 nm diameters, and correspond to the intraluminal vesicles of endosomal multivesicular bodies. Exosomes secreted by cells could micro-molecularly transfer messages between cells, and be the biological markers of cancer. In addition, exosomes could be collected in serum, tissue fluid and urine for diseases follow-up, and urine as the biosample is easier to repeatedly obtain and non-invasive. In this study, the investigators enroll patients with papillary, follicular, and collect the urine samples before operation, immediately after operation, post-operatively. The investigators try to analyze the urinary exosomal proteins to find the early prognostic biological markers in urine via this prospective study.

This pilot study report will explore that urinary exosomal thyroglobulin could be a reliable biological marker to substitute for serum thyroglobulin in the future. Such patient do not need to withdraw thyroid hormone or receive rhTSH stimulation. For patients with thyroid cancer, if they received thyroidectomy with ablative radioactive I-131 therapy, serum thyroglobulin is defined to be cancer biomarker in the course of follow-up. If thyroglobulin cannot be detected in serum, then such patients were suggested to be biochemically complete treatment, independent of the interference of anti-thyroglobulin antibody. Usually, serum thyroglobulin cannot be detected even under expensive rhTSH stimulation in patients of biochemically complete treatment. Therefore, no serial biomarkers could be recorded for evaluation and prediction of cancer recurrence. In this pilot study, urinary exosomal thyroglobulin provides a non-invasive, reproducible, convenient, serial and correct follow-up for patients with thyroid cancer, because the investigators use peptide sequence to quantify the levels of thyroglobulin in urine exosome. Significant reduction in cost-spending in rhTSH consumption, and patients do not need to stop using thyroid hormone during the course of cancer follow-up. In recent years, the progress of peptides mass spectrometry provided a cost-effective, correct and new pathway for the discovery of biomarkers. Large profiling of proteomics of human urine reveled different follow-up manners. In the viewpoints of oncology, one option is to find new biomarkers for earlier diagnosis of various cancers, and the other is to make a breakthrough for follow-up residual tumor and cancer recurrence. The goal of our pilot study is trying to find the new pathway for tracking the biomarker in patients with thyroid cancer receiving ablative surgery and radioactive I-131 treatment.