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

NCT06878534 | Recruiting

• 1 other identifier: 3/22
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Thyroid Cancer

Keywords

Thyroid Cancer, miRNA, non coding RNA

Outcome Measures

Primary Outcomes (2)

• Identification of novel molecular biomarkers associated with the progression and aggressiveness of follicular-derived thyroid carcinomas

  RNA-seq and miRNA-seq on serum samples

  1-36 months

• Determine genetic alterations hat may contribute to disease progression

  Identification of mutations, copy number variations, and tumor mutation burden)

  1-36 months

Secondary Outcomes (1)

• Develop of predictive models for improved risk stratification and prognosis

  12-36 months

Study Arms (2)

Thyroid cancer patients

Patients with thyroid cancer

Control subjects

Subjects with non-cancerous thyroid pathology

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with thyroid carcinoma originating from the follicular thyroid cell at varying degrees of malignancy. For such a retrospective population, considering the study's primary objective of identifying potential tissue biomarkers of pathology, an a posteriori power analysis was performed, considering a paired statistical design of the case-control type, where the control group is afferent to the healthy counterpart of the tissues available in the archives of the same thyroid carcinoma patients. For the subgroup analyses associated with the different degrees of invasiveness/aggressiveness, the statistical power associated with the possible clinical stratifications will be assessed before proceeding with the statistical analyses

You may qualify if:

• Patients of either sex aged \> 18 years with thyroid cancer of follicular origin.

Sponsors & Collaborators

• IRCCS SYNLAB SDN: lead
• University Federico II of Naples, Department of Clinical and Surgical Medicine: collaborator

Study Sites (1)

Irccs Synlab Sdn

Naples, 80146, Italy

RECRUITING

Related Publications (5)

• 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.

  PMID: 26462967 BACKGROUND

• 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.

  PMID: 35634500 BACKGROUND

• 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.

  PMID: 32284020 BACKGROUND

• 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.

  PMID: 33799953 BACKGROUND

• 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.

  PMID: 35020204 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum and Mononuclear cells from blood samples

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

• Giovanni Smaldone

  IRCCS SYNLAB SDN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Smaldone, Master degree in biothecnology

CONTACT

+39 0812408294; giovanni.smaldone@synlab.it

Laura Pierri

CONTACT

laura.pierri@synlab.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 17, 2025
• Study Start: March 13, 2023
• Primary Completion: July 30, 2024
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 17, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)