GenomicsNCT07532356
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
An observational study of Genomics and Thyroid Cancer, run by National Taiwan University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Genomics, Thyroid Cancer, NGS
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2026to 31 Jul 2031
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
This prospective clinical study is designed to enroll patients, aged between 18 to 80 years, with newly diagnosed papillary thyroid carcinoma (PTC) or highly suspicious follicular-pattern neoplasms, including lesions with potential for poorly differentiated thyroid carcinoma. Eligible patients must have undergone fine-needle aspiration cytology (FNAC) as part of the diagnostic work-up. (This is a routine examination that the subject would undergo regardless of study participation.) Cytological reports and subsequent comprehensive surgical pathology assessments will be systematically documented and reviewed to ensure accurate classification of each case. Across the first two years of study implementation, we aim to recruit 100 consecutive patients presenting with untreated, or "fresh," thyroid cancer. For individuals undergoing surgery, urinary exosomal peptide profiling will be conducted at two standardized time points: (1) preoperatively, and (2) four weeks after thyroidectomy, allowing assessment of perioperative biomarker dynamics. Surgical treatment-anticipated to be total thyroidectomy in most cases-will be performed according to standard clinical judgment by experienced endocrine surgeons. Postoperative pathological evaluation will include meticulous characterization of tumor morphology, invasion patterns, and molecular features, based on finalized histopathological reports. In parallel, this study incorporates a robust tumor genomic investigation supported by our previously developed and validated next-generation sequencing (NGS) platforms. Under prior funding from the National Science and Technology Council (NSTC), the investigators established a thyroid cancer-specific DNA-based gene panel targeting 50 key oncogenic drivers and a complementary RNA-based fusion panel covering 19 clinically relevant gene rearrangements. These panels were curated through comprehensive interrogation of internationally recognized cancer genomic repositories, based on previous successfully completed somatic variant profiling in 51 patients with metastatic thyroid cancer, including 29 paired primary-metastatic tumor analyses, demonstrating strong capability for high-resolution comparative cancer genomics. Furthermore, the investigators have established technical proficiency in polyguanine marker analysis for phylogenetic inference of tumor evolution, and have previously performed whole-genome sequencing (WGS) and HLA genotyping in large-scale association studies. Notably, the investigators' WGS-based investigations identified genetic susceptibility to antithyroid drug-induced agranulocytosis through a rigorous, two-stage analytic strategy. Overall, this integrated study design enables simultaneous evaluation of genomic initiation and progression alongside urinary exosomal peptide expression, positioning this work to elucidate mechanistic relationships between tumor molecular biology and non-invasive biomarkers for disease surveillance and precision-guided management.
- Conditions
- Genomics, Thyroid Cancer, NGS
- Keywords
- NGS, Urinary exosomal peptides, Differentiated thyroid cancer, Molecular recurrence surveillance, Risk stratification
- Medical subject headings
- Thyroid Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of serum thyroglobulin level
Thyroid function test
Measured: Within 12 months
Change of serum free T4 level
Thyroid function test
Measured: Within 12 months
Change of serum TSH level
Thyroid function test
Measured: Within 12 months
Change of anti-thyroglobulin level
Thyroid function test
Measured: Within 12 months
Urinary exosomal thyroglobulin detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal galectin-3 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal calprotectin A9 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal transketolase detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal keratin 19 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal angiopoietin-1 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal tissue inhibitor of metalloproteinase detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal keratin 8 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal calprotectin A8 detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal annexin II detection
Urinary exosomal biomarker
Measured: Within 12 months
Urinary exosomal afamin detection
Urinary exosomal biomarker
Measured: 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
Measured: Within 12 months
Pathology of post-operative thyroid tissue
- 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.
Measured: Within 12 months
Somatic Mutation Detection
detect somatic mutations
Measured: 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.
Measured: Within 12 months
Secondary outcomes (2)
Thyroid fine needle aspiration cytology
Thyroid function test
Measured: Within 12 months
Ultrasonography of thyroid nodules
Thyroid function test
Measured: Within 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2026
- Study start1 Aug 2026 (estimated)
- Primary completion31 Jul 2030 (estimated)
- Study completion31 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GenomicsStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- CHIH-YUAN WANG, Doctor, Principal investigator, Department of Internal Medicine, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07532356
- Sponsor's protocol ID
- 202602077RINC
- Status last verified
- Apr 2026
- First submitted
- 8 Apr 2026
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07532356
- Acronym / sponsor ID
- 202602077RINC
- Conditions
- Genomics, Thyroid Cancer, NGS
- Keywords
- NGS, Urinary exosomal peptides, Differentiated thyroid cancer, Molecular recurrence surveillance, Risk stratification
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Aug 2026 (estimated)
- Primary completion
- 31 Jul 2030 (estimated)
- Study completion
- 31 Jul 2031 (estimated)
- First posted
- 15 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This prospective clinical study is designed to enroll patients, aged between 18 to 80 years, with newly diagnosed papillary thyroid carcinoma (PTC) or highly suspicious follicular-pattern neoplasms, including lesions with potential for poorly differentiated thyroid carcinoma. Eligible patients must have undergone fine-needle aspiration cytology (FNAC) as part of the diagnostic work-up. (This is a routine examination that the subject would undergo regardless of study participation.) Cytological reports and subsequent comprehensive surgical pathology assessments will be systematically documented and reviewed to ensure accurate classification of each case. Across the first two years of study implementation, we aim to recruit 100 consecutive patients presenting with untreated, or "fresh," thyroid cancer. For individuals undergoing surgery, urinary exosomal peptide profiling will be conducted at two standardized time points: (1) preoperatively, and (2) four weeks after thyroidectomy, allowing assessment of perioperative biomarker dynamics. Surgical treatment-anticipated to be total thyroidectomy in most cases-will be performed according to standard clinical judgment by experienced endocrine surgeons. Postoperative pathological evaluation will include meticulous characterization of tumor morphology, invasion patterns, and molecular features, based on finalized histopathological reports. In parallel, this study incorporates a robust tumor genomic investigation supported by our previously developed and validated next-generation sequencing (NGS) platforms. Under prior funding from the National Science and Technology Council (NSTC), the investigators established a thyroid cancer-specific DNA-based gene panel targeting 50 key oncogenic drivers and a complementary RNA-based fusion panel covering 19 clinically relevant gene rearrangements. These panels were curated through comprehensive interrogation of internationally recognized cancer genomic repositories, based on previous successfully completed somatic variant profiling in 51 patients with metastatic thyroid cancer, including 29 paired primary-metastatic tumor analyses, demonstrating strong capability for high-resolution comparative cancer genomics. Furthermore, the investigators have established technical proficiency in polyguanine marker analysis for phylogenetic inference of tumor evolution, and have previously performed whole-genome sequencing (WGS) and HLA genotyping in large-scale association studies. Notably, the investigators' WGS-based investigations identified genetic susceptibility to antithyroid drug-induced agranulocytosis through a rigorous, two-stage analytic strategy. Overall, this integrated study design enables simultaneous evaluation of genomic initiation and progression alongside urinary exosomal peptide expression, positioning this work to elucidate mechanistic relationships between tumor molecular biology and non-invasive biomarkers for disease surveillance and precision-guided management.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Months
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of serum thyroglobulin level
Time frame: Within 12 months
Thyroid function test
Change of serum free T4 level
Time frame: Within 12 months
Thyroid function test
Change of serum TSH level
Time frame: Within 12 months
Thyroid function test
Change of anti-thyroglobulin level
Time frame: Within 12 months
Thyroid function test
Urinary exosomal thyroglobulin detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal galectin-3 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal calprotectin A9 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal transketolase detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal keratin 19 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal angiopoietin-1 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal tissue inhibitor of metalloproteinase detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal keratin 8 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal calprotectin A8 detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal annexin II detection
Time frame: Within 12 months
Urinary exosomal biomarker
Urinary exosomal afamin detection
Time frame: Within 12 months
Urinary exosomal biomarker
NGS assay
Time frame: Within 12 months
ultimately incorporated 50 mutation-targeted genes and 19 fusion-targeted genes known to contribute to the pathogenesis and clinical behavior of thyroid cancer
Pathology of post-operative thyroid tissue
Time frame: Within 12 months
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.
Somatic Mutation Detection
Time frame: Within 12 months
detect somatic mutations
Fusion Detection
Time frame: Within 12 months
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.
2 secondary outcomes
Thyroid fine needle aspiration cytology
Time frame: Within 12 months
Ultrasonography of thyroid nodules
Time frame: Within 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
CHIH-YUAN WANG, Doctor principal investigator
Department of Internal Medicine, National Taiwan University Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Genomics and Thyroid Cancer, run by National Taiwan University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CHIH-YUAN WANG, Doctor (+886-2-23123456 ext. 265371, cyw1965@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of serum thyroglobulin level (time frame: Within 12 months). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.