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

Обзор

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.

Первичные конечные точки

• Identification of novel molecular biomarkers associated with the progression and aggressiveness of follicular-derived thyroid carcinomas [Срок оценки: 1-36 months]
• Determine genetic alterations hat may contribute to disease progression [Срок оценки: 1-36 months]

Вторичные конечные точки (1)

• Develop of predictive models for improved risk stratification and prognosis [Срок оценки: 12-36 months]

Критерии участия

Критерии включения

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

Критерии исключения

• Patients who do not fit the inclusion criteria.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• Irccs Synlab Sdn — Naples

Публикации

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• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06878534 · 3/22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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