Integrating Tumor Genomics and Urinary Exosomal Proteomics to Establish a Multi-Layer Biomarker Framework for Early Risk Stratification and Post-Treatment Surveillance in Fresh Thyroid Cancer Patients

NCT07532356 | Not Yet Recruiting

• 1 other identifier: 202602077RINC
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Thyroid cancer is the most common endocrine malignancy, and although differentiated thyroid cancer (DTC) generally confers favorable outcomes, 10-20% of patients still face substantial postoperative risks, including local recurrence, distant metastasis, and inadequate response to radioactive iodine therapy. Current risk stratification, largely based on tumor size, lymph node involvement, and histopathology, fails to adequately represent tumor heterogeneity and evolutionary changes, potentially resulting in both overtreatment and undertreatment. Next-generation sequencing (NGS) has revealed a stepwise accumulation of genomic alterations from early driver mutations (e.g., BRAF, RAS, RET/PTC, PAX8-PPARG) to late-stage progression events (e.g., TERT promoter, TP53, PI3K/AKT/mTOR), while metastatic lesions often harbor high-risk mutations absent in primary tumors, underscoring the limitations of single-time-point tissue sampling. Furthermore, serum thyroglobulin (Tg) surveillance is hindered in patients with anti-Tg antibodies. Extracellular vesicles (EVs), particularly those obtained from urine, provide a compelling liquid biopsy modality due to their non-invasiveness, repeatability, and reduced interference by abundant serum proteins. The investigators' previous findings demonstrate that urinary exosomal peptides-including U-Ex Tg, ANXA2, TIMP, and Angiopoietin-1-correlate with malignancy, capsular invasion, and nodal metastasis, and exhibit dynamic postoperative variation, suggesting their utility in detecting molecular residual disease. This prospective study will recruit 100 fresh thyroid cancer cases and integrate tumor genomic profiling, urinary exosomal proteomics via LC-MRM/MS, and clinical phenotype assessment-including nodal involvement, subsequent therapies, and long-term outcomes-to delineate causal links between genomic drivers, proteomic execution signals, and clinical progression. The overarching aim is to establish an early risk-stratification and molecular recurrence-alerting model capable of identifying high-risk trajectories earlier than conventional approaches, thereby enhancing surveillance precision and enabling timely intervention. This multi-layered biomarker framework holds strong potential to redefine postoperative monitoring standards and advance the clinical and policy implementation of precision medicine in thyroid cancer.

Conditions

Genomics; Thyroid Cancer; NGS

Keywords

NGS; Urinary exosomal peptides; Differentiated thyroid cancer; Molecular recurrence surveillance; Risk stratification

Outcome Measures

Primary Outcomes (19)

• Change of serum thyroglobulin level

  Thyroid function test

  Within 12 months

• Change of serum free T4 level

  Thyroid function test

  Within 12 months

• Change of serum TSH level

  Thyroid function test

  Within 12 months

• Change of anti-thyroglobulin level

  Thyroid function test

  Within 12 months

• Urinary exosomal thyroglobulin detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal galectin-3 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal calprotectin A9 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal transketolase detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal keratin 19 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal angiopoietin-1 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal tissue inhibitor of metalloproteinase detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal keratin 8 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal calprotectin A8 detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal annexin II detection

  Urinary exosomal biomarker

  Within 12 months

• Urinary exosomal afamin detection

  Urinary exosomal biomarker

  Within 12 months

• NGS assay

  ultimately incorporated 50 mutation-targeted genes and 19 fusion-targeted genes known to contribute to the pathogenesis and clinical behavior of thyroid cancer

  Within 12 months

• Pathology of post-operative thyroid tissue

  1\) Tumor type; 2) Tumor size and volume; 3) Encapsulation; 4) Surgical margin involvement: nearest distance to surgical margin; 5) Capsular invasion; 6) Angioinvasion (Vascular invasion); 7) Lymphatic invasion; 8) Extra-thyroidal extension; 9) lymphocytic thyroiditis background; 10) TNM staging; 11) Distribution of lymph nodes metastatic over neck (Level I -VI); 12) Immunohistochemical staining: BRAFV600E, PAX8, TERT, HBME-1 and Galectin-3.

  Within 12 months

• Somatic Mutation Detection

  detect somatic mutations

  Within 12 months

• Fusion Detection

  To characterize the mutational landscape across different histological subtypes of thyroid cancer and to investigate intra-patient spatial genomic heterogeneity between primary and metastatic tumors, as well as to evaluate the clinical relevance of these molecular differences.

  Within 12 months

Secondary Outcomes (2)

• Thyroid fine needle aspiration cytology

  Within 12 months

• Ultrasonography of thyroid nodules

  Within 12 months

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Prospectively initiating enroll 100 newly diagnosed Differentiated thyroid cancer (DTC) patients undergoing surgery using standardized SOPs. Perform fresh-tissue next-generation sequencing (NGS) using a thyroid cancer-specific gene fusion/mutation panel. Collect paired urine samples preoperatively and at postoperative status according to a harmonized sampling schedule.

You may qualify if:

• Aged 18 to 80 years
• Newly diagnosed Papillary Thyroid Carcinoma (PTC) or highly suspected follicular thyroid neoplasms (including lesions with potential progression to poorly differentiated thyroid carcinoma)
• Pre-operative status

You may not qualify if:

• Aged \<18 or \>80 years
• No confirmed diagnosis of Papillary Thyroid Carcinoma (PTC)
• No highly suspected follicular thyroid neoplasms (including lesions with potential progression to poorly differentiated thyroid carcinoma)

Sponsors & Collaborators

• National Taiwan University Hospital: lead

MeSH Terms

Conditions

Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• CHIH-YUAN WANG, Doctor

  Department of Internal Medicine, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CHIH-YUAN WANG, Doctor

CONTACT

+886-2-23123456; cyw1965@gmail.com

PEI-JIE HUANG, Bachelor

CONTACT

+886-2-23123456; pylaff1920@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2031
• Last Updated: April 20, 2026

Record last verified: 2026-04