Observational Study Analysing the Transcriptome and Mutational Status of Thyroid Carcinomas of Follicular Origin with Different Degrees of Malignancy

NCT ID: NCT06878534

Last Updated: 2025-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-03-13

Study Completion Date

2027-03-31

Brief Summary

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Thyroid cancer (TC) is the most common endocrine malignancy, with well-differentiated thyroid carcinomas (DTCs)-papillary (PTC) and follicular (FTC)-comprising the majority of cases. While DTCs generally have favorable prognoses, a subset progresses to poorly differentiated or anaplastic thyroid carcinoma (ATC), which is highly aggressive. Tumor classification is based on histopathology, invasiveness, and molecular characteristics, with new entities like thyroid tumors of uncertain malignant potential (TT-UMP) and non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) refining diagnostic criteria.

Current standard treatments include surgical resection, radioactive iodine therapy, and thyroid hormone replacement. However, some patients develop radioiodine-refractory disease with an increased risk of recurrence and progression. Molecular alterations in the MAPK and PI3K pathways play critical roles in thyroid tumorigenesis, influencing therapeutic response and prognosis. Identifying novel biomarkers for early detection and risk stratification is crucial. Emerging evidence highlights the role of microRNAs (miRNAs) in thyroid cancer progression, functioning as oncogenes or tumor suppressors.

This retrospective case-control study aims to identify novel molecular markers linked to thyroid cancer aggressiveness. Archived formalin-fixed paraffin-embedded (FFPE) tissue and blood samples will be analyzed from patients with varying degrees of PTC and FTC invasiveness. Control samples will be histologically normal thyroid tissue from the same patients.

Next Generation Sequencing (NGS), including RNA-seq and miRNA-seq, will be employed to detect differentially expressed RNA molecules. Validation will be performed using Real-Time PCR in an independent cohort. High-throughput genomic sequencing (Illumina TruSight Oncology 500) will assess mutations, copy number variations, and tumor mutation burden to correlate genetic alterations with malignancy. Variants will be prioritized based on frequency differences in tumor vs. non-tumor populations and functional relevance.

The study will enroll patients with follicular cell-derived thyroid carcinoma. A power analysis indicates that 80 subjects provide \>80% statistical power for biomarker identification. Descriptive statistics, parametric/non-parametric tests, and machine learning approaches will analyze transcriptomic and genomic data. Receiver operating characteristic (ROC) curves will assess diagnostic biomarker accuracy, while logistic regression will model associations between molecular alterations and disease severity.

This study aims to uncover molecular mechanisms driving thyroid cancer progression and identify biomarkers for improved risk stratification, early diagnosis, and potential therapeutic targeting. Findings may enhance personalized treatment approaches in thyroid oncology.

Detailed Description

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Conditions

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Thyroid Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Thyroid cancer patients

Patients with thyroid cancer

No interventions assigned to this group

Control subjects

Subjects with non-cancerous thyroid pathology

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Patients of either sex aged \> 18 years with thyroid cancer of follicular origin.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Federico II of Naples, Department of Clinical and Surgical Medicine

UNKNOWN

Sponsor Role collaborator

IRCCS SYNLAB SDN

OTHER

Sponsor Role lead

Responsible Party

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Marco Salvatore

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Giovanni Smaldone

Role: PRINCIPAL_INVESTIGATOR

IRCCS SYNLAB SDN

Locations

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Irccs Synlab Sdn

Naples, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Giovanni Smaldone, Master degree in biothecnology

Role: CONTACT

+39 0812408294

Laura Pierri

Role: CONTACT

Facility Contacts

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Laura Pierri

Role: primary

Laura Pierri

Role: backup

References

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Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.

Reference Type BACKGROUND
PMID: 26462967 (View on PubMed)

Rossi ED, Locantore P, Bruno C, Dell'Aquila M, Tralongo P, Curatolo M, Revelli L, Raffaelli M, Larocca LM, Pantanowitz L, Pontecorvi A. Molecular Characterization of Thyroid Follicular Lesions in the Era of "Next-Generation" Techniques. Front Endocrinol (Lausanne). 2022 May 12;13:834456. doi: 10.3389/fendo.2022.834456. eCollection 2022.

Reference Type BACKGROUND
PMID: 35634500 (View on PubMed)

Xu B, Fuchs T, Dogan S, Landa I, Katabi N, Fagin JA, Tuttle RM, Sherman E, Gill AJ, Ghossein R. Dissecting Anaplastic Thyroid Carcinoma: A Comprehensive Clinical, Histologic, Immunophenotypic, and Molecular Study of 360 Cases. Thyroid. 2020 Oct;30(10):1505-1517. doi: 10.1089/thy.2020.0086. Epub 2020 May 8.

Reference Type BACKGROUND
PMID: 32284020 (View on PubMed)

Macerola E, Poma AM, Vignali P, Basolo A, Ugolini C, Torregrossa L, Santini F, Basolo F. Molecular Genetics of Follicular-Derived Thyroid Cancer. Cancers (Basel). 2021 Mar 7;13(5):1139. doi: 10.3390/cancers13051139.

Reference Type BACKGROUND
PMID: 33799953 (View on PubMed)

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.

Reference Type BACKGROUND
PMID: 35020204 (View on PubMed)

Other Identifiers

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3/22

Identifier Type: -

Identifier Source: org_study_id

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