Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3
Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3
Although thyroid cancers are low-grade endocrine malignancy, most patients usually received
 thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with
 thyroid ultrasonography and serial serum thyroglobulin evaluation. Prior researches indicated
 that one-third well-differentiated thyroid cancers could transform to poorly-differentiated
 patterns, even to be anaplastic thyroid cancer (ATC), a fatal malignancy, and no effective
 therapeutic strategies was noted, including surgical intervention, chemotherapy and
 radiotherapy. The poorly-differentiated or anaplastic change of thyroid cancer cells
 proliferates rapidly and always invades local tissues with distant metastasis. Cellular
 de-differentiation is the most pivotal cause for malignant transformation and invasion.
 De-differentiation usually in papillary thyroid cancer and follicular thyroid cancer, and
 definitely in ATC. Therefore, the investigators try to find the biological markers and
 therapeutic targets via the exosomal expression in urine. On the continuing basis of prior
 ATC cells culture experiments.

 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. The investigators try to analyze the urinary exosomal proteins, including
 thyroglobulin and galectin-3, to find the early prognostic biological markers in urine via
 this prospective study.

 The investigators expected to enroll 150 post-operative patients with papillary, follicular
 or anaplastic thyroid cancer, and collect the urine samples in outpatient clinic per year.
 The investigators will analyze the urine exosomal proteins and probable biological markers,
 including thyroglobulin and galectin-3. The investigators hope to find the prognostic
 biological markers via this prospective study. The investigators further hope to find newly
 therapeutic and follow-up pathway for such patients with well-differentiated or anaplastic
 thyroid cancer.
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.
Inclusion Criteria:diagnosed patients with thyroid papillary, follicular and anaplastic
 thyroid cancer, post-operation follow up

 -

 Exclusion Criteria:

 -  Unclearly diagnosed patients with thyroid papillary, follicular and anaplastic thyroid
 cancer